The motives for the predominance of S. aureus in SA and the mechanisms of pathogenecity are not however fully understood. The synovium of individuals with RA is rich in IL 1.We’ve previously shown that S. aureus can bind to IL 1 and use it as a development aspect. A current report by McLaughlin and Hoogewerf showed that the growth and replication of S. aureus in a biofilm are considerably elevated by the addition of rhIL 1.We’ve got also observed that rhIL 1 can modulate the gene expression in S. aureus including the bicomponent leukotoxins and some on the surface adhesion molecules collectively referred to as MSCRAMMs in addi tion to some of the genes within the pathogenecity island of S. aureus. We speculate that the IL 1 wealthy synovial milieu could possibly potentially contribute for the elevated frequency of S.
aureus in patients with RA SA and that the host derived MMPs induced by S. aureus may accelerate the pathogenesis of SA. Our data on the induction of MMPs by S. aureus culture super natants and cell lysates compares properly with the prior report selleck by Williams and colleagues, who demonstrated MMP 1 and three expression by articular cartilage upon exposure to puri fied culture supernatant from S. aureus. We have extended this observation by showing expression of a wide selection of MMPs, including MMP 7, by human synovial also as der mal fibroblasts in response to S. aureus components. The pro file was equivalent to that induced by a combination of IL 1 TNF, which could indicate the involvement of an inflammatory cytokine mediated pathway inside the observed induction of MMPs by S. aureus. S.
aureus culture supernatants and cell lysates have a wide variety of proteins, and identification on the compound libraries for drug discovery components that are truly accountable for inducing the MMP induction is essential to figure out the mechanisms of induction as well as to rationally design intervening agents against bacterial prod ucts. Toward this we finish, we’ve got narrowed down the possi ble candidates to molecular weight groups of your selection of 30 to 50 determined by our experiments making use of Centricon filtration of your culture supernatants. Because the molecular weight on the chemically purified PGN utilized in previous studies just isn’t recognized, we’re not inside a position to ascertain irrespective of whether PGN is incorporated in the stated molecular weight range.
At this time, we’ve not identified the elements beyond the molecular level, nonetheless, this guidelines out the possibility of a few of the recently described low molecular weight proteins for example the 19 kDa extracellular fibrinogen binding protein that inhibits complement activation. Specific complement elements have already been reported to activate MMPs. The results from the fractionated supernatants also tentatively rule out the possibil ity of the exotoxin akin towards the toxic shock syndrome protein described by Ren and colleagues as well as the enterotoxin H described by Su and Wong.