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Background: Viral myocarditis (VMC) plays a significant role in heart failure, and there is currently a shortage of available targeted treatments. Macrophage phenotype and function are closely associated with the beta‐2 adrenergic receptor (β2‐AR). Method: This research employed a BALB/c mouse model of VMC generated using Coxsackievirus B3 (CVB3), and the β2‐AR agonist formoterol was administered as treatment. A bioinformatic analysis was conducted to identify the β2‐AR in CCR2+MHCIIhigh monocyte‐derived macrophages (MoMFs). Echocardiography and histopathological assessments were utilized to evaluate cardiac function and inflammation. The enzymatic activity of glutaminase (GLS) was quantified. Flow cytometry was employed to characterize the phenotype and function of the macrophages. Result: Our study revealed that formoterol treatment effectively mitigated cardiac inflammation and fibrosis, improved cardiac function, and prolonged survival compared to the VMC group. Formoterol reduced the infiltration of CCR2+MHCIIhigh MoMFs in the heart, inhibited M1 phenotypic expression and activity, and reduced the percentage of Ly6Chigh monocytes in circulation. Additionally, formoterol stimulated M2 phenotypic expression and activity and increased the percentage of Ly6Clow monocytes in circulation. Additionally, the combination of NICB3344, a C‐C motif chemokine receptor 2 inhibitor, with formoterol did not exhibit synergistic effects on reducing cardiac pathological scores or enhancing cardiac function. In vitro studies involving the use of lipopolysaccharide (LPS)‐induced bone marrow‐derived macrophages, revealed the ability of formoterol to suppress the M1 phenotype and functions induced by LPS while promoting the M2 phenotype and functions. Nevertheless, the observed effects were negated by the introduction of the GLS inhibitor BPTES. Conclusion: Formoterol potentially serves as a significant metabolic regulator in the differentiation process of cardiac MoMFs, influencing this process by controlling GLS activity. Targeting β2‐AR exhibits potential as an effective approach for managing VMC. It is essential to acknowledge that these findings were derived under specific experimental conditions, with the current conclusions predominantly based on animal models. Future research is necessary to further investigate the feasibility of formoterol in clinical practice. [ABSTRACT FROM AUTHOR]

G protein‐coupled receptors (GPCRs) are membrane‐bound signaling proteins that play an essential role in cellular signaling processes. Due to their intrinsic function of transmitting internal signals in response to external cues, these receptors are adapted to be highly dynamic in nature. The β2‐adrenergic receptor (β2AR) is a representative member of the family that has been extensively analyzed in terms of its structure and activation. Although the structure of the transmembrane domain has been characterized in the different functional states of the receptor, the conformational dynamics of the extramembrane domains, especially the intrinsically disordered regions are still emerging. In this study, we analyze the state‐dependent dynamics of extramembrane domains of β2AR using atomistic molecular dynamics simulations. We introduce a parameter, the residue excess dynamics that allows us to better quantify receptor dynamics. Using this measure, we show that the dynamics of the extramembrane domains are sensitive to the receptor state. Interestingly, the ligand‐bound intermediate R′ state shows the maximal dynamics compared to either the active R*G or inactive R states. Ligand binding appears to be correlated with high residue excess dynamics that are dampened upon G protein coupling. The intracellular loop‐3 (ICL3) domain has a tendency to flip towards the membrane upon ligand binding, which could contribute to receptor "priming." We highlight an important ICL1‐helix‐8 interplay that is broken in the ligand‐bound state but is retained in the active state. Overall, our study highlights the importance of characterizing the functional dynamics of the GPCR loop domains. [ABSTRACT FROM AUTHOR]

Introduction: Allergic diseases are mediated by T helper cell type 2 (Th2) cells, which are differentiated by dendritic cells (DCs). Recently, it was reported that cAMP concentration in DCs is important for inducing allergic responses. However, the regulatory function of cAMP in DCs in Th2 immune responses is unclear. It was hypothesized that the regulation of G protein-coupled receptors (GPCRs) to increase cAMP levels in DCs would reduce Th2 immune responses. Methods: Human DCs from patients with allergic rhinitis (AR) and from healthy controls were subjected to next-generation sequencing (NGS) to identify potential GPCR. To investigate the functions of GPCR agonists, the in vitro co-culture experiment that THP-1 cells were differentiated into DCs and cultured with human CD4+ T-cells and an AR animal in vivo model were used. Results: Among the GPCRs, the beta-2 adrenergic receptor (ADRB2) of allergic DCs was significantly increased by NGS analysis. The expression of ADRB2 was also increased in Der p 1-treated DCs, which was reduced by treatment with the ADRB2 agonist salbutamol. Salbutamol treatment induced cAMP production in THP-1 derived DCs. In an in vitro co-culture experiment, salbutamol-treated DCs reduced the secretion of Th2 cytokine. In an in vivo AR animal experiment, salbutamol-administered mice showed reduced allergic behavior and Th2 cytokine expression in the nasal mucosa. Conclusions: The regulation of ADRB2 with salbutamol alleviated the allergic response in vitro DC-T cell co-culture and in vivo AR animal models, suggesting that ADRB2 is a therapeutic target for AR and that ADRB2 agonists may be a promising medication for AR. [ABSTRACT FROM AUTHOR]

The usage of beta blockers in breast cancer (BC) patients is implicated in the reduction in distant metastases, cancer recurrence, and cancer mortality. Studies suggest that the adrenergic pathway is directly involved in sympathetic-driven hematopoietic activation of pro-tumor microenvironmental proliferation and tumor cell trafficking into the circulation. Cancer-associated macrophage-like cells (CAMLs) are pro-tumor polynucleated monocytic cells of hematopoietic origin emanating from tumors which may aid in circulating tumor cell (CTC) dissemination into the circulation. We examined the linkage between Beta-2 adrenergic receptor (B2AR) signaling in CAMLs and CTCs by establishing expression profiles in a model BC cell line (MDA-MB-231). We compared the model to CAMLs and CTCs found in patents. Although internalization events were observed in patients, differences were found in the expression of B2AR between the tumor cell lines and the CAMLs found in patients. High B2AR expression on patients' CAMLs was correlated with significantly more CAMLs in the circulation (p = 0.0093), but CTCs had no numerical relationship (p = 0.1565). High B2AR CAML expression was also significantly associated with a larger size of CAMLs (p = 0.0073), as well as being significantly associated with shorter progression-free survival (p = 0.0097) and overall survival (p = 0.0265). These data suggest that B2AR expression on CAMLs is closely related to the activation, intravasation, and growth of CAMLs in the circulation. [ABSTRACT FROM AUTHOR]

Communication between the nervous and immune systems serves a key role in host‐protective immunity at mucosal barrier sites including the respiratory tract. In these tissues, neuroimmune interactions operate in bidirectional circuits that can sense and respond to mechanical, chemical, and biologic stimuli. Allergen‐ or helminth‐induced products can produce airway inflammation by direct action on nociceptive afferents and adjacent tissues. The activity of nociceptive afferents can regulate innate and adaptive immune responses via neuropeptides and neurotransmitter signaling. This review will summarize recent work investigating the role of neuropeptides CGRP, VIP, neuromedins, substance P, and neurotransmitters dopamine and the B2‐adrenoceptor agonists epinepherine/norepinepherine, each of which influence type 2 immunity by instructing mast cell, innate lymphoid cell type 2, dendritic cell, and T cell responses, both in the airway and the draining lymph node. Afferents in the airway also contain receptors for alarmins and cytokines, allowing their activity to be modulated by immune cell secreted products, particularly those secreted by mast cells. Taken together, we propose that further investigation of how immunoregulatory neuropeptides shape respiratory inflammation in experimental systems may reveal novel therapeutic targets for addressing the increasing prevalence of chronic airway disease in humans. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to compare the beta-2 adrenergic receptor (ADRB2) gene polymorphisms of patients with fibromyalgia syndrome (FMS) with those of healthy control subjects, and to investigate the possible relationship between symptoms of FMS and polymorphisms of the ADRB2 gene. Patients and methods: The study included 170 females (mean age 47.8±10.3 years; range, 21 to 75 years) diagnosed with FMS according to the 2010 American College of Rheumatology criteria and 170 healthy females (mean age 47.2±8.8 years; range, 20 to 72 years) as the control group. Several clinical symptoms of the participants related to FMS were questioned and recorded. The visual analog scale (VAS) and Fibromyalgia Impact Questionnaire (FIQ) scores of the fibromyalgia group were recorded. In both groups, the ADRB2 (rs1042717) single-nucleotide polymorphism was detected by way of a real-time polymerase chain reaction. The wild-type (Guanine/Guanine), the mutant type (Adenine/Adenine) and heterozygous type (Adenine/Guanine) were detected. The sample power was calculated considering the minor allele frequency. Results: The comparison of the ADRB2 gene polymorphism between patients with FMS and the control subjects showed that the groups were similar in terms of ADBR2 gene polymorphism and genotype (p>0.05). There was no significant difference in terms of genotype when the ADRB2 gene polymorphisms in patients with FMS were compared in terms of clinical symptoms, VAS and FIQ scores (p>0.05). Conclusion: Beta-2 adrenergic receptor (rs1042717) gene polymorphisms and genotype distribution are no different between patients with FMS and healthy individuals. ADRB2 gene polymorphisms in patients with FMS have no effect on clinical symptoms and VAS and FIQ scores. The results of the present study will light the way for future research into ADRB2 gene polymorphisms in the pathogenesis of FMS. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphism is responsible for variations and individual differences. Polymorphism is a major factor of complex diseases with unknown etiology and cancer. Inconsistency in the symptoms of polycystic ovary syndrome (monthly disorder, hirsutism, obesity, diabetes, infertility) is one of the major pathological complications of this syndrome. The present study was conducted to evaluate the polymorphism gene β2 and β3 adrenergic receptors in women with polycystic ovary syndrome. Methods: This cross-sectional study was performed on 200 patients with polycystic ovary syndrome (PCOS) in Imam Khomeini Hospital, Vali-e-Asr Infertile Clinic in Tehran, Iran, from March 2016 to April 2017. Blood samples in two groups (study and control) were obtained for genomics approved by the DNA Company based on the gene bank. Polymerase chain reaction (PCR) samples were extracted and then the primer design was performed by using Primer Express software, version 3.0 (Applied Biosystems, Foster City, CA, USA) and confirmed by using of the primer blast tool at the NCBI site in terms of compliance with the beta 3 adrenergic receptor gene. Analysis of protein changes was performed by using CLUSTALW (https://www.genome.jp/toolsbin/ clustalw). Polymorphism was investigated on codons 16, 27, 113 and 164 from the beta2 adrenoceptor gene and codon 64 of the beta3 adrenergic receptor gene. Results: The study of the codon beta2 of adrenoceptors showed that only codon 164 (Thr164Ile) polymorphism (44.4%) was significant (P<0/002) in study group. Homozygote and heterozygote ratios also show a significant difference between the study and control groups (P<0/004). Polymorphism exon 1 in codon 64 of beta3 adrenoceptor; which codes the amino acid tryptophan, indicates that the nucleotide T has changed to C. This finding confirms that mutagenic genotype can raise chance of getting to the polycystic ovary syndrome in women. OR: 2.546 (95% CI: 1.02-5.367) (P=0.012). Conclusion: These results show that polymorphisms of codon 164 (Thr164Ile) of beta2 receptor gene and beta3 adrenergic receptor gene polymorphism Thr164Ile (rs 4994) associate with polycystic ovary syndrome and the risk of PCOS are significantly increased in mutation genotype women. [ABSTRACT FROM AUTHOR]

The β2-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB2function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in theADRB2gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β2-agonists in COPD. We searched the medical literature from 1966 to 2017 and found 16 relevant studies comprising 85381 study subjects. The meta-analyses found no significant association betweenADRB2genotype and COPD risk. The summary odds ratios (ORs) for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence interval (CI): 0.54–12.4) and 1.17 (95% CI: 0.96–1.44), respectively. Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were 0.97 (95% CI: 0.76–1.22) and 1.01 (95% CI: 0.81–1.26), while summary ORs for COPD in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80–1.25) and 0.94 (95% CI: 0.69–1.24), respectively. When stratified by ethnicity, the summary ORs for COPD did not differ from 1.0 for any of theADRB2variants among Asian, Caucasian, or African populations. We found no consistent associations betweenADRB2genotype and treatment response to inhaled β2-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β2-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rareADRB2genotypes are required. [ABSTRACT FROM AUTHOR]

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Summary: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms influence receptor function. We show that these polymorphisms are not associated with fracture risk or bone mineral density in the UCP, Rotterdam Study, and GEFOS cohorts. Introduction: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms are known to influence receptor function in vitro and in vivo (rs1042713, rs1042714, and rs1800888). We examined the role of these polymorphisms in the B2AR gene on human bone metabolism. Methods: We performed nested case-control studies to determine the association of these polymorphisms with fracture risk in the Utrecht Cardiovascular Pharmacogenetics (UCP) cohort and in three cohorts of the Rotterdam Study. We also determined the association of these polymorphisms with bone mineral density (BMD) in the GEFOS Consortium. UCP contains drug-dispensing histories from community pharmacies linked to national registrations of hospital discharges in the Netherlands. The Rotterdam Study is a prospective cohort study investigating demographics and risk factors of chronic diseases. GEFOS is a large international collaboration studying the genetics of osteoporosis. Fractures were defined by ICD-9 codes 800-829 in the UCP cohort (158 cases and 2617 unmatched controls) and by regular X-ray examinations, general practitioner, and hospital records in the Rotterdam Study (2209 cases and 8559 unmatched controls). BMD was measured at the femoral neck and lumbar spine using dual-energy X-ray absorptiometry in GEFOS ( N = 32,961). Results: Meta-analysis of the two nested case-control studies showed pooled odds ratios of 0.98 (0.91-1.05, p = 0.52), 1.04 (0.97-1.12, p = 0.28), and 1.16 (0.83-1.62, p = 0.38) for the associations between rs1042713, rs1042714, and rs1800888 per minor allele and fractures, respectively. There were no significant associations of the polymorphisms and BMD in GEFOS. Conclusion: In conclusion, polymorphisms in the beta-2 adrenergic receptor gene are not associated with fracture risk or BMD. [ABSTRACT FROM AUTHOR]

Aim To describe the clinical and histopathological characteristics of infantile haemangiomas that failed treatment with oral propranolol . Design This study is a case series from the vascular birthmarks clinic at Royal Children's Hospital, Melbourne. Patients The patients for this study were infants who commenced treatment with oral propranolol before 6 months of age and who were treated for at least 4 months without a satisfactory result. For histology and immunohistochemistry, tissue from the four non-responding patients who subsequently underwent surgical excision was matched with four historical controls. Outcome measures Based on medical record review and photographic assessments, infants were defined as having failed treatment with oral propranolol if the infantile haemangioma either continued to grow or showed 20% improvement or less. Tissue sections were examined for tissue structure, mast cells, sympathetic innervations and beta-2 adrenergic receptor expression, and the number of mast cells and beta-2 adrenergic positive cells. Results From a group of 135 infants who met the inclusion criteria, 14 infants failed propranolol treatment. Eleven of these infants had focal facial haemangiomas. No difference was seen in tissue morphology, tissue innervations, beta-2 adrenergic receptor expression, cell number or mast cell distribution, and number between non-responding and control haemangiomas. Conclusion We report a treatment failure rate of 10%, which is higher than previously reported. Focal facial lesions failed to respond twice as frequently as other types of haemangioma. No histopathological reason was identified to indicate why some haemangiomas failed to respond. [ABSTRACT FROM AUTHOR]

Abstract: The beta-2 adrenergic receptor (β2AR) has a carboxyl terminus motif that can interact with PSD-95/discs-large/ZO1 homology (PDZ) domain-containing proteins. In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel binding partner of β2AR. The carboxyl terminus of β2AR binds with high affinity to the fifth PDZ domain of MAGI-3, with the last four amino acids (D-S-L-L) of the receptor being the key determinants of the interaction. In cells, the association of full-length β2AR with MAGI-3 occurs constitutively and is enhanced by agonist stimulation of the receptor. Our data also demonstrated that β2AR-stimulated extracellular signal-regulated kinase-1/2 (ERK1/2) activation was substantially retarded by MAGI-3 expression. These data suggest that MAGI-3 regulates β2AR-mediated ERK activation through the physical interaction between β2AR and MAGI-3. Structured summary: MINT-7716556: beta2AR (uniprotkb:P07550) physically interacts (MI:0915) with MAGI-3 (uniprotkb:Q5TCQ9) by anti tag coimmunoprecipitation (MI:0007) MINT-7716593: beta2AR (uniprotkb:P18762) physically interacts (MI:0915) with MAGI-3 (uniprotkb:Q9EQJ9) by anti bait coimmunoprecipitation (MI:0006) MINT-7716630: MAGI-3 (uniprotkb:Q5TCQ9) and beta2AR (uniprotkb:P07550) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7716382, MINT-7716335: MAGI-3 (uniprotkb:Q5TCQ9) physically interacts (MI:0915) with beta2AR (uniprotkb:P07550) by pull down (MI:0096) MINT-7716320, MINT-7716422, MINT-7716502, MINT-7716450, MINT-7716470: beta2AR (uniprotkb:P07550) binds (MI:0407) to MAGI-3 (uniprotkb:Q5TCQ9) by pull down (MI:0096) [Copyright &y& Elsevier]

Beta-2-Adrenergic receptors (β2AR) participate in the physiologic responses of the lung, including bronchodilation and bronchoprotection, through mechanisms such as mucociliary clearance, fluid accumulation and mediator release from mast cells and basophils. Thus, these receptors may also play an important role in the pathophysiology of asthma. The gene encoding β2AR ( ADRB2) is extremely polymorphic, and studies of this gene improves our understanding of asthma and possibly lead to new methods to prevent, diagnose and treat it. This review summarizes results from various studies on the possible relationship of ADRB2 polymorphisms to asthma and asthma-related phenotypes, including bronchodilator responses to inhaled β2-agonists. At present, it appears that, for asthma, ADRB2 polymorphisms are not aetiologically involved. However, they might affect disease severity and clinical response to both acute and chronic administration of β2-agonists. The development is that by assessing the ADRB2 genotype, it might be possible to predict the clinical course of asthma as well as responsiveness to chronic administration of β2-agonists. Carefully, performed and adequately powered clinical trials continue to be important for achieving those goals. [ABSTRACT FROM AUTHOR]

Objectives: The beta-2 adrenergic receptor is involved in mediating vasodilatation via neurohumoral and sympathetic nervous system pathways. Alterations in beta-2 adrenergic receptor gene expression (mRNA transcription) may contribute to the hypertensive phenotype. Human gene expression in clinical phenotypes remains largely unexplored due to ethical constraints involved in obtaining human tissue. We devised a method to obtain normally discarded internal mammary artery tissue from coronary artery bypass graft patients. We then investigated differences in hypertensive and normotensive participants' beta-2 adrenergic receptor gene expression in this tissue. Methods: We collected arterial tissue samples from 46 coronary artery bypass patients in a surgical setting. Using 41 of the samples, we performed TaqMan real-time polymerase chain reaction (RT-PCR) and used the delta delta cycle threshold (ΔΔCt) relative quantitation method for determination of fold-differences in gene expression between normotensive and hypertensive participants. The beta-2 adrenergic receptor target was normalized to glyceraldehyde-phosphate dehydrogenase. Results: Participants with hypertension had significantly less-expressed beta-2 adrenoceptor gene (2.76-fold, p < .05) compared to normotensive participants. After Bonferroni correction, gene expression did not differ by race, gender, type/dose of β-blocker prescribed, positive family history of hypertension, or diagnosis of diabetes mellitus type 2. Conclusions: These data support the possibility of a molecular basis for impaired adrenoceptor-mediated vascular tone in hypertension. Modification and extension of this research is required. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Adipose tissue distribution (visceral vs subcutaneous) has been shown to be an important predictor of insulin resistance, diabetes and cardiovascular disease, independent of body mass index. The beta-2 adrenergic receptor is a major lipolytic receptor in human fat cells and the gene that codes for this protein is an important candidate gene for measures of adiposity and fat deposition. We examined whether two common polymorphisms in codons 16 (Arg16Gly) and 27 (Gln27Glu) are associated with measures of fat distribution in participants of the IRAS Family Study. METHODS:: We recruited African-American (AA) and Hispanic-American (HA) families from Los Angeles, CA, USA (18 pedigrees, 272 AA individuals), San Antonio, TX, USA (33 pedigrees, 448 HA individuals) and San Luis Valley, CO, USA (12 pedigrees, 272 HA individuals). We estimated adipose tissue distribution via computed tomography. To test for an association between adiposity measures and these polymorphisms, we used generalized estimating equations, adjusting for age, gender, clinical site (ethnicity), body mass index, and familial correlation. RESULTS:: Of the 992 individuals genotyped for these polymorphisms, 57%were female and 15%had been diagnosed with type 2 diabetes mellitus. The mean age was 42.7±14.6?y. The Glu27 allele of the Gln27Glu polymorphism was positively associated with (P-value for recessive model): body mass index (0.025), visceral adipose tissue (<0.0001) and visceral-to-subcutaneous adipose ratio (0.009), but not with subcutaneous adipose tissue (0.952). The Arg16Gly polymorphism was not associated with any of the adiposity measures. CONCLUSIONS:: These findings suggest that genetic variation in the beta-2 adrenergic receptor gene influences fat deposition and body size in AAs and HAs. In particular, these results support a role for the gene in the distribution of visceral adipose tissue but not subcutaneous adipose tissue.International Journal of Obesity (2005) 29, 449-457. doi:10.1038/sj.ijo.0802883 Published online 18 January 2005 [ABSTRACT FROM AUTHOR]

We studied the distribution of the rat brain beta-2 adrenergic receptor (AR) mRNA, and the effects of monoamine depletions by chronic reserpine treatment using in situ hybridization histochemistry. In the control group, high level signals of beta-2 AR mRNA were observed in the parietal, frontal and piriform cortices, the medial septal nuclei, the olfactory tubercle, and the midbrain. Moderate signals were found in the striatum, the retrosplenial cortex, the hippocampus, and the thalamic nuclei. After chronic reserpine treatment, beta-2 AR mRNA levels were increased in many brain regions. The large increases were seen in the hippocampus, all thalamic nuclei, the amygdaloid nuclei, and the midbrain, followed by the striatum and the occipital cortex. The receptor up-regulation resulting from chronic monoamine depletion may be due to these increases in beta-2 AR mRNA, indicating that this up-regulation may be caused by increased receptor production rather than decreased receptor degradation. [ABSTRACT FROM AUTHOR]

Background: The potency of T regulatory (TREG) cells to inhibit T helper (Th)-driven immune cell responses has been linked to increased intracellular cyclic-AMP (cAMP) levels of TREG cells. In an ovalbumin (OVA)-driven allergic asthma mouse model, moderate aerobic exercise increases TREG cell function in a contact-dependent manner that leads to a significant reduction in chronic inflammation and restoration of lung function. However, the mechanism, whereby exercise increases TREG function, remains unknown and was the focus of these investigations. Exercise can communicate with TREG cells by their expression of β2-adrenergic receptors (β2-AR). Activation of these receptors results in an increase in intracellular levels of cyclic-AMP, potentially creating a potent inhibitor of Th cell responses. Results: For the allergic asthma model, female wildtype BALB/c mice were challenged with OVA, and exercised (13.5 m/min for 45 min) 3×/week for 4 weeks. TREG cells were isolated from all mouse asthma/exercise groups, including β2-AR−/− mice, to test suppressive function and intracellular cAMP levels. In these studies, cAMP levels were increased in TREG cells isolated from exercised mice. When β2-AR expression was absent on TREG cells, cAMP levels were significantly decreased. Correlatively, their suppressive function was compromised. Next, TREG cells from all mouse groups were tested for suppressive function after treatment with either a pharmaceutical β2-adrenergic agonist or an effector-specific cAMP analogue. These experiments showed TREG cell function was increased when treated with either a β2-adrenergic agonist or effector-specific cAMP analogue. Finally, female wildtype BALB/c mice were antibody-depleted of CD25+CD4+ TREG cells (anti-CD25). Twenty-four hours after TREG depletion, either β2-AR−/− or wildtype TREG cells were adoptively transferred. Recipient mice underwent the asthma/exercise protocols. β2-AR−/− TREG cells isolated from these mice showed no increase in TREG function in response to moderate aerobic exercise. Conclusion: These studies offer a novel role for β2-AR in regulating cAMP intracellular levels that can modify suppressive function in TREG cells. [ABSTRACT FROM AUTHOR]