Search

Background Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. Objectives We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. Methods We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro –differentiated human nasal epithelial cells cultured at air-liquid interface. Results As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Conclusions Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity.

This chapter discusses chronic inflammation, as shown in asthma and other disorders of the airways. Investigation into the use of the drug artesunate is documented as a powerful drug in the remedy of many different kinds of inflammatory diseases beyond its antimalaria application. The text suggests that more in-depth work is required to investigate the pathways regulated by artesunate in disease models. Further molecular analysis is needed to identify potential molecular markers. Resources are provided for further results of studies on the anti-inflammatory role of artesunate.

Pollution of phthalates, including di-(2-ethylhexyl)phthalate (DEHP), is widespread because of their use in plastics and other daily consumer products. Epidemiological studies have shown that the largest source of general population exposure to DEHP is on dietary. Studies have suggested an association between exposure to phthalate plasticisers, and increased prevalence of asthma. To investigate the adjuvant effect of DEHP on asthmatic pathological changes in ovalbumin-immunised rat model. Wistar rats were randomly divided into five groups (eight rats of each group): (1) saline; (2) ovalbumin (OVA); (3) OVA+DEHP 0.7mg·kg−1·d−1; (4) OVA+DEHP 70 mg·kg−1·d−1; and (5) DEHP 70 mg·kg−1·d−1. DEHP treatment groups which were administered to 0.7 mg and 70 mg DEHP/kg/d by gastric gavage for 30d before and during the process of OVA immunisation or saline treatment. The in vivo pulmonary function analysis, bronchoalveolar lavage (BAL) fluid collection and section histological observation were conducted. DEHP ...

Increased airway smooth muscle (ASM) mass is believed to underlie the relatively fixed airway hyperresponsiveness (AHR) in asthma. Developments of therapeutic approaches to reverse airway remodeling are impeded by our lack of insight on the mechanisms behind the increase in mass of contractile ASM cells. Increased expression of laminin, an extracellular matrix protein, is associated with asthma. Our studies investigate the role of laminin-induced ASM survival signals in the development of increased ASM and AHR. Antagonizing laminin integrin binding using the laminin-selective competing peptide, YIGSR, and mimicking laminin with exogenous α2-chain laminin, we show that laminin is both necessary and sufficient to induce ASM cell survival, concomitant with the induction of ASM contractile phenotype. Using siRNA, we show that the laminin-binding integrin α7β1 mediates this process. Moreover, in laminin-211-deficient mice, allergen-induced AHR was not observed. Notably, ASM cells from asthmatic airways express a higher abundance of intracellular cell survival proteins, consistent with a role for reduced rates of cell apoptosis in development of ASM hyperplasia. Targeting the laminin-integrin α7β1 signaling pathway may offer new avenues for the development of therapies to reduce the increase in mass of contractile phenotype ASM cells that underlie AHR in asthma.—Tran, T., Teoh, C. M., Tam, J. K. C., Qiao, Y., Chin, C. Y., Chong, O. K., Stewart, A. G., Harris, T., Wong, W. S. F., Guan, S. P., Leung, B. P., Gerthoffer, W. T., Unruh, H., and Halayko, A. J. Laminin drives survival signals to promote a contractile smooth muscle phenotype and airway hyperreactivity.

Background Airway smooth muscle (ASM) contraction underpins airway constriction; however, underlying mechanisms for airway hyperresponsiveness (AHR) remain incompletely defined. CD151, a 4-transmembrane glycoprotein that associates with laminin-binding integrins, is highly expressed in the human lung. The role of CD151 in ASM function and its relationship to asthma have yet to be elucidated. Objective We sought to ascertain whether CD151 expression is clinically relevant to asthma and whether CD151 expression affects AHR. Methods Using immunohistochemical analysis, we determined the expression of CD151 in human bronchial biopsy specimens from patients with varying asthma severities and studied the mechanism of action of CD151 in the regulation of ASM contraction and bronchial caliber in vitro , ex vivo , and in vivo . Results The number of CD151 + ASM cells is significantly greater in patients with moderate asthma compared with those in healthy nonasthmatic subjects. From loss- and gain-of-function studies, we reveal that CD151 is required for and enhances G protein–coupled receptor (GPCR)–induced peak intracellular calcium release, the primary determinant of excitation-contraction coupling. We show that the localization of CD151 can also be perinuclear/cytoplasmic and offer an explanation for a novel functional role for CD151 in supporting protein kinase C (PKC) translocation to the cell membrane in GPCR-mediated ASM contraction at this site. Importantly, CD151 −/− mice are refractory to airway hyperreactivity in response to allergen challenge. Conclusions We identify a role for CD151 in human ASM contraction. We implicate CD151 as a determinant of AHR in vivo , likely through regulation of GPCR-induced calcium and PKC signaling. These observations have significant implications in understanding the mechanism for AHR and the efficacy of new and emerging therapeutics.

The dynamics of aboveground biomass and stem volume in subalpine coniferous Picea asperata plantations with different stand ages in 70 years of artificial restoration process were studied by adopting the concept of space as a substitute for time. The results indicated that before 20 years of stand age, the biomass of spruce single tree grew quite slow, with that of the twigs and needles accounting for about 50%; after 20 years, it increased obviously, with 60% of biomass accumulated in stem; from 30 to 40 years, the increasing rate of biomass relatively slowed down, and maintained a rapid growth after 40 years. The biomass of spruce population showed a similar trend, though the period of relative slow-down of growth continued from 30 to 50 years. For the biomass of community as a whole, it presented a general continuous increase, but varied greatly for different layers. In shrub layer, the biomass rose rapidly at the early stage of plantation establishment and gradually decreased after 20 years, while that of the herbaceous plants reduced continuously and accounted less than 0.2% of the total biomass of community when the stand reached 70 years. Both the mean annual increment and the current annual increment of stem volume of spruce single tree went up with the increasing stand age, and more rapidly at the later stages. Similar changes were observed for the stock volume of the plantations, with the only difference that the current annual increment from 30 to 50 years was relatively reduced. Based on the data from stem analysis and growth ring measurement, regression models of stem volume with DBH and tree height of 70 years Picea asperata plantation were established.