Anti-S100A8 monoclonal antibody, clone JNH59N8D8

Ulcerative colitis (UC) is one chronically remittent and progressive inflammatory disorder. Chemokine receptor CXCR2 is reported to be involved in the pathogenesis of several inflammatory diseases. However, how CXCR2 modulate mucosal inflammation in UC is still obscure. In this study, CXCR2 expression was determined in inflamed mucosa and peripheral blood cells from patients with UC by qRT-PCR. Neutrophils isolated from peripheral blood were pretreated with CXCR2 inhibitor (SB225002), and proinflammatory mediators were examined by qRT-PCR, ELISA and IF. The migratory capacity of neutrophils after SB225002 treatment was examined by using Transwell plate. Furthermore, SB225002 was administrated daily in DSS-induced colitis mice. We found that CXCR2 expression was significantly increased in colonic mucosal tissues and peripheral blood cells from patients with active UC. Besides, CXCR2 was highly expressed in neutrophils, and was positively correlated with disease activity. Inhibition of CXCR2 in neutrophils decreased the production of proinflammatory mediators, such as reactive oxygen species (ROS), MPO, S100a8, S100a9, TNF-alpha, IL-1 beta, IL-8 and IL-6, and the migratory capacity of neutrophils was markedly impaired after SB225002 treatment. Moreover, blockade of CXCR2 with SB225002 could markedly ameliorate DSS-induced colitis in mice. In summary, CXCR2 plays a critical role in the pathogenesis of UC through modulating immune responses of neutrophils. Blockade of CXCR2 may serve as a new therapeutic approach for treatment of UC.

In patients with interstitial pneumonia, pulmonary fibrosis is an irreversible condition that can cause respiratory failure. Novel treatments for pulmonary fibrosis are necessary. Inflammation is thought to activate lung fibroblasts, resulting in pulmonary fibrosis. Of the known inflammatory molecules, we have focused on S100A8/A9 from the onset of inflammation to the subsequent progression of inflammation. Our findings confirmed the high expression of S100A8/A9 in specimens from patients with pulmonary fibrosis. An active role of S100A8/A9 was demonstrated not only in the proliferation of fibroblasts but also in the fibroblasts' differentiation to myofibroblasts (the active form of fibroblasts). S100A8/A9 also forced fibroblasts to upregulate the production of collagen. These effects were induced via the receptor of S100A8/A9, i.e., the receptor for advanced glycation end products (RAGE), on fibroblasts. The anti-S100A8/A9 neutralizing antibody inhibited the effects of S100A8/A9 on fibroblasts and suppressed the progression of fibrosis in bleomycin (BLM)-induced pulmonary fibrosis mouse model. Our findings strongly suggest a crucial role of S100A8/A9 in pulmonary fibrosis and the usefulness of S100A8/A9-targeting therapy for fibrosis interstitial pneumonia.