دانلود رایگان مقاله ارزیابی تضعیف کننده ایمنی بالقوه پپتید گریزان

Abstract

A previously studied immunosuppressive cytokine, Soluble Immune Response Suppressor (SIRS), may have relevance to current studies of immune suppression in a variety of human disease states. Despite extensive efforts using experimental models, mainly in mice, much remains to be discovered as to how autoimmune cells in mice and humans escape normal regulation and, conversely, how tumor cells evade evoking an immune response. It is the contention of this commentary that the literature pre-2000 contain results that might inform current studies. The broadly immunosuppressive protein, SIRS, was studied extensively from the 1970s to 1990s and culminated in the determination of the n-terminal 21mer sequence of this 15 kDa protein which had high homology to the short neurotoxins from sea snakes, that are canonical members of the three finger neurotoxin superfamily (3FTx). It was not until 2007 that the prophylactic administration of the synthetic N-terminal peptide of the SIRS 21mer, identical to the published sequence, was reported to inhibit or delay the development of two autoimmune diseases in mice: experimental allergic encephalomyelitis (EAE) and type I diabetes (T1D). These findings were consistent with other studies of the 3FTx superfamily as important probes in the study of mammalian pharmacology. It is the perspective of this commentary that SIRS, SIRS peptide and the anti-peptide mAb, represent useful, pharmacologically-active probes for the study of the immune response as well as in the potential treatment of autoimmune, inflammatory diseases and cancer.

4. Conclusions

Data on SIRS from the 1970s to 1990s describe a potent immunosuppressive protein induced by antigens, mitogens, interferons and infectious agents that is present in both mice and humans. It has a potential mechanism of action involving the disruption of microtubule formation in a variety of cell types. The SIRS peptide also has pharmacological activity [54,55]. The elusive nature of this peptide and the present mystery surrounding its genetic origin, including its possible link to the 3FTx toxin superfamily, suggests that the time is ripe to revisit this nearly forgotten cytokine by tapping into the exponential growth in genomics data obtained from a wide variety of species since the SIRS peptide was sequenced more than 25 years ago. Thus, it is not unreasonable to expect that a focused reanalysis of human and murine databases might lead to the identification of the genetic source of SIRS in mammals as has been done for virtually every other known protein cytokine [96]. For reasons that remain unclear, this protein seems to be an exception leading to the questions: Why? And how did this sequence emerge from an extract obtained from a murine T cell hybridoma? A deeper genomic analysis using newer tools to probe the genome database has yet to provide a clear answer (Noordewier and Webb, unpublished data).