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Active repressors have been evidenced to function in different plant growth and development programs including hormonal signalling pathways. In Arabidopsis, the MYB-bHLH-WDR (MBW) complex is known to regulate different phenotypic traits such as anthocyanin biosynthesis, seed coat colour, trichome and root hair patterning. A number of transcription factors have been identified to play a negative role in the regulation of these traits via the interruption of MBW formation and function. Since these transcription factors work to interfere with the MBW complex, this review suggests their general name as MBW interferers (MBWi). Recent studies have shed light on the molecular mechanism of these MBWi and this review is aiming to provide a precise view of these MBWi. Moreover, from these, a new characteristic of active repressors is also updated.

The auxin signaling and root morphogenesis are harmoniously controlled by two counteracted teams including (1) auxin/indole-3-acetic acid (AUX/IAA)-histone deacetylase (HDA) and (2) auxin response factor (ARF)-histone acetyltransferase (HAT). The involvement of histone acetylation in the regulation of transcription was firstly reported a few decades ago. In planta, auxin is the first hormone group that was discovered and it is also the most studied phytohormone. Current studies have elucidated the functions of histone acetylation in the modulation of auxin signaling as well as in the regulation of root morphogenesis under both normal and stress conditions. Based on the recent outcomes, this review is to provide a hierarchical view about the functions of histone acetylation in auxin signaling and root morphogenesis. In this report, we suggest that the auxin signaling must be controlled harmoniously by two counteracted teams including (1) auxin/indole-3-acetic acid (AUX/IAA)-histone deacetylase (HDA) and (2) auxin response factor (ARF)-histone acetyltransferase (HAT). Moreover, the balance in auxin signaling is very critical to contribute to normal root morphogenesis.

Streptococcus pneumoniae (pneumococcus) is responsible for significant morbidity and mortality worldwide. It causes a variety of life-threatening infections such as pneumonia, bacteremia, and meningitis. In bacterial physiology, the metabolic pathway of branched-chain amino acids (BCAAs) plays an important role in virulence. Nonetheless, the function of IlvC, one of the enzymes involved in the biosynthesis of BCAAs, in S. pneumoniae remains unclear. Here, we demonstrated that downregulation of BCAA biosynthesis by ilvC ablation can diminish BCAA concentration and expression of pneumolysin (Ply) and LytA, and subsequently attenuate virulence. Infection with an ilvC mutant showed significantly reduced mortality and colonization in comparison with strain D39 (serotype 2, wild type), suggesting that ilvC can potentiate S. pneumoniae virulence due to adequate BCAA synthesis. Taken together, these results suggest that the function of ilvC in BCAA synthesis is essential for virulence factor and could play an important role in the pathogenesis of respiratory infections.

Free radicals and other oxidants are critical determinants of the cellular signaling pathways involved in the pathogenesis of several human diseases including inflammatory diseases. Numerous studies have demonstrated the protective effects of antioxidant enzymes during inflammation by elimination of free radicals. The superoxide dismutase (SOD), an antioxidant enzyme, plays an essential pathogenic role in the inflammatory diseases by not only catalyzing the conversion of the superoxide to hydrogen peroxide and oxygen but also affecting immune responses. There are three distinct isoforms of SOD, which distribute in different cellular compartments such as cytosolic SOD1, mitochondrial SOD2, and extracellular SOD3. Many studies have investigated the anti-oxidative effects of SOD3 in the inflammatory diseases. Herein, in this review, we focus on the current understanding of SOD3 as a therapeutic protein in inflammatory diseases such as skin, autoimmune, lung, and cardiovascular inflammatory diseases. Moreover, the mechanism(s) by which SOD3 modulates immune responses and signal initiation in the pathogenesis of the diseases will be further discussed.

The innate and adaptive arms of the immune system tightly regulate immune responses in order to maintain homeostasis and host defense. The interaction between those two systems is critical in the activation and suppression of immune responses which if unchecked may lead to chronic inflammation and autoimmunity. γδ T cells are non-conventional lymphocytes, which express T cell receptor (TCR) γδ chains on their surface and straddle between innate and adaptive immunity. Recent advances in of γδ T cell biology have allowed us to expand our understanding of γδ T cell in the dysregulation of immune responses and the development of autoimmune diseases. In this review, we summarize current knowledge on γδ T cells and their roles in skin and joint inflammation as commonly observed in rheumatic diseases.

Flavonoids are members of polyphenolic compounds, which are naturally presented in fruits, vegetables, and some medicinal plants. Traditionally, the root of Scutellaria baicalensis is widely used as Chinese herbal medicine and contains several major bioactive compounds such as Wogonin, Scutellarein, Baicalein, and Baicalin. Experimental and clinical evidence has been proving that Wogonin exhibits diverse biological activities such as anti-cancer, anti-inflammation, and treatment of bacterial and viral infections. In this review, we summarize and emphasize the benefits of Wogonin as a therapeutic adjuvant for anti-viral infection, anti-inflammation, neuroprotection as well as anxiolytic and anticonvulsant. Moreover, the molecular mechanism(s) how Wogonin mediates the cellular signal pathways and immune responses are also discussed and highlighted valuable properties of Wogonin in multiple therapies.

Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease. In this study, we investigated the effect of superoxide dismutase 3 (SOD3) on P. acnes- or peptidoglycan (PGN)-induced inflammation in vitro and in vivo. Our data demonstrated that SOD3 suppressed toll-like receptor-2 (TLR-2) expression in P. acnes- or PGN-treated keratinocytes and sebocytes. Moreover, we found that SOD3 suppressed the expressions of phosphorylated nuclear factor-κB (NF-κB) and p38 in P. acnes- or PGN-treated cells. SOD3 also exhibited an anti-inflammatory role by reducing the expression of inflammasome-related proteins (NLRP3, ASC, caspase-1) and inhibiting the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8. In addition, SOD3 reduced lipid accumulation and expression of lipogenic regulators in P. acnes-treated sebocytes. Recombinant SOD3-treated wild-type mice and SOD3 transgenic mice, which were subcutaneously infected with P. acnes, showed tolerance to inflammation through reducing inflammatory cell infiltration in skin, ear thickness, and expression of inflammatory mediators. Our result showed that SOD3 could suppress the inflammation through inhibition of TLR2/p38/NF-κB axis and NLRP3 inflammasome activation. Therefore, SOD3 could be a promising candidate for treatment of P. acnes-mediated skin inflammation.

Activating transcription factor-3 (ATF3) acts as a negative regulator of cytokine production during Gram-negative bacterial infection. A recent study reported that ATF3 provides protection from Streptococcus pneumoniae infection by activating cytokines. However, the mechanism by which S. pneumoniae induces ATF3 after infection is still unknown. In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. Induction was mediated by TLR4 and TLR2, which are in the TLR family. The expression of ATF3 was induced by pneumolysin (PLY), a potent pneumococcal virulence factor, via the TLR4 pathway. Furthermore, ATF3 induction is mediated by p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Thus, this study reveals a potential role of PLY in modulating ATF3 expression, which is required for the regulation of immune responses against pneumococcal infection in macrophages.

Streptococci cause a variety of diseases, such as dental caries, pharyngitis, meningitis, pneumonia, bacteremia, endocarditis, erysipelas, and necrotizing fasciitis. The natural niche of this genus of bacteria ranges from the mouth and nasopharynx to the skin, indicating that the bacteria will inevitably be subjected to environmental changes during invasion into the host, where it is exposed to the host immune system. Thus, the Streptococcus-host interaction determines whether bacteria are cleared by the host's defenses or whether they survive after invasion to cause serious diseases. If this interaction was to be deciphered, it could aid in the development of novel preventive and therapeutic agents. Streptococcus species possess many virulent factors, such as peroxidases and heat-shock proteins (HSPs), which play key roles in protecting the bacteria from hostile host environments. This review will discuss insights into the mechanism(s) by which streptococci adapt to host environments. Additionally, we will address how streptococcal infections trigger host stress responses; however, the mechanism by which bacterial components modulate host stress responses remains largely unknown.

Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae , including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae , as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (Δ adhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H 2 O 2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the Δ adhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the Δ adhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence.

Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (Δ clpL ) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.

Background Activating transcription factor-3 (ATF3) is known as a suppressor of cytokine production after exposure to lipopolysaccharide or during gram-negative bacterial infection. However, the mechanism by which ATF3 regulates innate immunity against gram-positive bacterial infection, particularly Streptococcus pneumoniae, remains unknown. Methods The wild-type and ATF3 knock-out (KO) mice were infected intranasally (i.n) or intraperitoneally with S. pneumoniae, and bacterial colonization or survival rate was determined. Pneumococcal pneumonia was induced by i.n infection, and ATF3 level was determined by Western blot. ATF3 KO cells or ATF3 siRNA transfection were used to determine expression of ATF3 downstream genes. Enzyme-linked immunosorbent assay was used to examine cytokines levels. Results ATF3 was highly expressed in various cell lines in vitro and in many organs in vivo. Pneumolysin was a novel inducer of ATF3. Pneumococcal infection induced ATF3, which subsequently stimulated production of cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and interferon [IFN]-γ). ATF3-mediated cytokine induction protected the host from pneumococcal infection. In the pneumonia infection model, the bacterial clearance of wild-type mice was more efficient than those of ATF3 KO mice. Conclusions Taken together, we can conclude that ATF3 regulates innate immunity positively upon pneumococcus infection by enhancing TNF-α, IL-1β, and IFN-γ expression and modulating bacterial clearance.

Activating transcription factor 3 (ATF3) is a stress-induced transcriptional regulator in eukaryote. The role of ATF3 in cancer has been well defined, but how ATF3 functions in bacterial infection is not well understood. Pneumococcal infection has been shown to induce ATF3 expression, which subsequently enhances cytokine production and provides protection from lethal Streptococcus pneumoniae infection, but the role of ATF3 in other Gram-positive (G(+)) infections remains unclear. Here, we report that infection with other G(+) bacteria (Staphylococcus aureus and Listeria monocytogenes) and with G(-) bacteria (uropathogenic Escherichia coli) also significantly induced ATF3 expression. Moreover, the production of cytokines (tumor necrosis factor alpha [TNF]-α, interleukin [IL]-1β, IL-6 and interferon [IFN]-γ) was enhanced by ATF3 in S. aureus and L. monocytogenes infection, but decreased in uropathogenic E. coli (UPEC) infection. In addition, in S. aureus and L. monocytogenes infections, ATF3 WT mice cleared bacteria more efficiently and had higher survival rates than ATF3 knockout mice. However, in UPEC infection, no significant difference was found in survival rate. Taken together, these data suggest that ATF3 provides protection from S. aureus and L. monocytogenes infections; however, the role of ATF3 in UPEC infection is more complicated and should be further elucidated.