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NLRC5, the largest member of the Nod‐like receptor (NLR) family, has been reported to play a pivotal role in regulating inflammatory responses. Recent evidence suggests that NLRC5 participates in Toll‐like receptor (TLR) signaling pathways and negatively modulates nuclear factor‐κB (NF‐κB) activation. In this study, we investigated the interaction between NLRC5 and TLR2 in the NF‐κB inflammatory signaling pathway and the involvement of NLRC5 in TLR2‐mediated allergic airway inflammation. We knocked down TLR2 and NLRC5, respectively in the RAW264.7 macrophage cell line by small interfering RNA (siRNA) and then stimulated the knockdown cells with lipoteichoic acid (LTA). In comparison with the negative siRNA group, the level of NLRC5 expression was lower in the TLR2 siRNA group, with a reduction in the NF‐κB‐related inflammatory response. Conversely, in the NLRC5 knockdown cells, after LTA‐treated the level of TLR2 expression did not change but the expression levels of both NF‐κB pp65 and NLRP3 increased remarkably. Thus, we hypothesize that NLRC5 participates in the LTA‐induced inflammatory signaling pathway and regulates the inflammation via TLR2/NF‐κB. Similarly, in subsequent in vivo experiments, we demonstrated that the expression level of NLRC5 was significantly increased in the ovalbumin‐induced allergic airway inflammation. However, this effect disappeared in TLR2‐deficient (TLR2 −/−) mice and was accompanied by reduced levels of NF‐κB expression and airway inflammation. In conclusion, NLRC5 negatively regulates LTA‐induced inflammatory response via a TLR2/NF‐κB pathway in macrophages and also participates in TLR2‐mediated allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Galectin-1 (Gal-1) has immunomodulatory activities in various allergic inflammatory disorders, but its potential anti-inflammatory properties on allergic airway diseases have not been confirmed. We explored the pharmacological effects of Gal-1 on the progression of allergic airway inflammation and investigated the underlying mechanism. Female C57BL/6 mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-17 to establish an allergic airway inflammation model. In the challenge phase, a subset of mice was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). We found that rGal-1 inhibited pulmonary inflammatory cell recruitment, mucus secretion, bronchoalveolar lavage fluid (BALF) inflammatory cell infiltration, and cytokine production. The treatment also suppressed the infiltration of eosinophils into the allergic lung as indicated by decreased expression levels of eotaxin and eosinophil peroxidase (EPX). However, only the expression levels of IL-25, neither IL-33 nor TSLP, were significantly decreased in the lung by rGal-1 treatment. These immunomodulatory effects in the allergic lung were correlated with the activation of extracellular signal-regulated kinase (ERK) signaling pathway and downregulation of endogenous Gal-1. In addition, rGal-1 reduced the plasma concentrations of anti-OVA immunoglobulin E (IgE) and IL-17. Our findings suggest that rGal-1 is an effective therapy for allergic airway inflammation in a murine model and may be a potential pharmacological target for allergic airway inflammatory diseases. [ABSTRACT FROM AUTHOR]