Periodontitis is a chronic inflammatory disorder caused by specific bacteria residing in the biofilm, particularly Porphyromonas gingivalis (Pg). Sprouty2 (Spry2) functions as a negative regulator of the fibroblast growth factor (FGF) signaling pathway. We previously demonstrated that sequestration of Spry2 induced proliferation and osteogenesis in osteoblastic cells by basic FGF (bFGF) and epidermal growth factor (EGF) stimulation in vitro, but diminished cell proliferation in gingival epithelial cells. In addition, Spry2 knockdown in combination with bFGF and EGF stimulation increases periodontal ligament cell proliferation and migration accompanied by prevention of osteoblastic differentiation. In this study, we investigated the mechanisms through which Spry2 depletion by interferon (IFN) γ and Pg lipopolysaccharide (LPS) stimulation affected the physiology of macrophages in vitro. Transfection of macrophages with Spry2 small‐interfering RNA (siRNA) promoted the expression of genes characteristic of M2 alternative activated macrophages, induced interleukin (IL)‐10 expression, and enhanced arginase activity, even in cells stimulated with IFNγ and Pg LPS. In addition, we found that phosphoinositide 3‐kinase (PI3K) and AKT activation by Spry2 downregulation enhanced efferocytosis of apoptotic cells by increasing Rac1 activation and decreasing nuclear factor kappa B (NFκB) p65 phosphorylation but not signal transducer and activator of transcription 1 (STAT1) phosphorylation. Collectively, our results suggested that topical administration of Spry2 inhibitors may efficiently resolve inflammation in periodontal disease as macrophage‐based anti‐inflammatory immunotherapy and may create a suitable environment for periodontal wound healing. These in vitro findings provide a molecular basis for new therapeutic approaches in periodontal tissue regeneration.
Although various observations (1-5) have failed to relate serum antibody to resistance against tuberculosis, these findings need not preclude a role for humorM factors in an as yet indeterminate and possibly rather complex pattern of resistance. The participation of humoral factors in resistance to tubercle bacilli was indicated by the observation that the sera of animals immunized with the BCG strain of tubercle bacillus contained a substance which protected the monocytes of these immunized animals against the necrotizing action of virulent tubercle bacilli (6). While the protective substance was found in immune and not in normal sera, its activity was seemingly non-specific in nature, for the immune sera of animals immunized with antigens totally unrelated to the tubercle bacillus (Salmonella, Brucdla, ovalbumin) proved equally effective in protecting the monocytes of BCG-immunized animals against virulent tubercle bacilli (7, 8). It was also found that these immune sera protected the monocytes of the BCG-immunized animal but failed to afford similar protection to normal monocytes (6).Studies of cellular resistance showed that it was also not entirely specific, since, in the presence of immune sera, the monocytes of animals immunized with either Mycobacterium or Brucdla proved partially or completely resistant to heterologous as well as homologous infection (8). Despite the seeming lack of specificity suggested by the cross-immunity between the cells of animals immunized with Brucella and Mycobacterium some selectivity of action was demonstrable in cells; thus, while both anti-Brucdla and anti-Salmonella sera contained a substance which protected the cells of BCG-immunized animals against virulent tubercle bacilli, the monocytes of the Brucella-and Salmonellaimmunized animals behaved quite differently in that the cells of the Salmonellaimmunized animal proved completely susceptible to virulent tubercle bacilli (7).
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