The reasons for the predominance of S. aureus in SA as well as the mechanisms of pathogenecity aren’t yet totally understood. The synovium of individuals with RA is rich in IL 1.We have previously shown that S. aureus can bind to IL 1 and use it as a growth factor. A current report by McLaughlin and Hoogewerf showed that the development and replication of S. aureus within a biofilm are considerably enhanced by the addition of rhIL 1.We’ve also observed that rhIL 1 can modulate the gene expression in S. aureus like the bicomponent leukotoxins and some in the surface adhesion molecules collectively known as MSCRAMMs in addi tion to some of the genes in the pathogenecity island of S. aureus. We speculate that the IL 1 rich synovial milieu may well potentially contribute for the improved frequency of S.
aureus in sufferers with RA SA and that the host derived MMPs induced by S. aureus could possibly accelerate the pathogenesis of SA. Our information around the induction of MMPs by S. aureus culture super natants and cell lysates compares nicely using the earlier report additional resources 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’ve got extended this observation by showing expression of a wide range of MMPs, which includes MMP 7, by human synovial at the same time as der mal fibroblasts in response to S. aureus elements. The pro file was equivalent to that induced by a combination of IL 1 TNF, which may 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 possess a wide assortment of proteins, and identification on the selleck chemicals components which can be really responsible for inducing the MMP induction is essential to identify the mechanisms of induction also as to rationally design intervening agents against bacterial prod ucts. Toward this we end, we’ve narrowed down the possi ble candidates to molecular weight groups on the selection of 30 to 50 determined by our experiments making use of Centricon filtration of the culture supernatants. Since the molecular weight on the chemically purified PGN employed in preceding research just isn’t identified, we’re not inside a position to establish whether or not PGN is included within the stated molecular weight range.
At this time, we have not identified the elements beyond the molecular level, nevertheless, this guidelines out the possibility of some of the recently described low molecular weight proteins for instance the 19 kDa extracellular fibrinogen binding protein that inhibits complement activation. Particular complement elements happen to be reported to activate MMPs. The outcomes with 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 and the enterotoxin H described by Su and Wong.