Proinflammatory chemoattractants

Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ (2000) Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165 6519-6524 Widmer U, Manogue KR, Cerami A, Sherry B (1993) Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. J Immunol 150 4996-5012 Ye RD (2001) Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. [Review] [136 refs]. J Leukoc Biol 70 839-848... 

IL-17 induces the production of IL-8 in endothelial and parenchymal cells, indicating an indirect role in PMN recruitment. IL-8 is a potent chemoattractant for polymorphonuclear neutrophils (PMN) and can also stimulate the release of neutrophil granules and the respiratory burst of these cells [5,71-78]. In their study, Kostulas et al. found that the proinflammatory cytokine IL-17 was elevated systemically after ischemic stroke. IL-17 induces the secretion of cytokines, including IL-8, and enhances the expression of ICAM-1 in cultures of stromal cells and human fibroblasts [5,77,79]. 

Elicitation is the clinical response to subsequent challenge with the antigen or hapten. Penetration into the skin leads to encounters with antigen-specific memory T cells. These cells release cytokines such as IFN-y and IL-17 that recruit other cells to the site and stimulate the production of chemoattractants and proinflammatory cytokines (e.g., IL-8, IL-1, TNF-a, IL-6) from multiple cell types, including T cells and keratinocytes. The resulting effect is an infiltration of inflammatory cells into the tissue and a localized increase in vascular permeability leading to... 

Chemoattractant properties are the major biological effect of CKs. Their receptors are G protein-coupled receptors that form a family of structurally and functionally related proteins. CKs are induced in cells and tissue in response to proinflammatory cytokines. They are produced by a large diversity of cells (Figure 22-32). The CK superfamily, with the exception of RANTES, p-TG, HCC-1, and PF-4, is not expressed in resting cells but is rapidly induced in response to various inflammatory and mitogenic stimuli. Probably all CKs have some activities that are unique and many that are... 

The other broad category of MSP actions on macrophages relates to mediator production. Endotoxin, or combinations of proinflammatory cytokines, causes expression of murine macrophage-inducible nitric oxide synthase, an effect that can be detected by Northern blots for the mRNA or by measurement of nitrate in the culture fluid. MSP prevents induction of NO-synthase by any of the above stimuli (Wang et al., 1994d). The inhibitory action of MSP is confined to this specific mediator. MSP did not inhibit endotoxin-induced expression of mRNA for monocyte chemoattractant protein-1. Furthermore, MSP caused secretion of IL-6 (but not IL-1 or TNFa) within 6 hr, and did not inhibit endotoxin-induced secretion of IL-1, IL-6, or TNFa (A. Skeel and E. J. Leonard, unpublished data). The in vitro modulation by MSP of endotoxin-induced NO production now has an in vivo counterpart. Concentrations of nitrate in serum of Stk / mice that received endotoxin intravenously were higher than in serum of comparably treated normal mice and at a critical endotoxin dose, only 20% of the Stk / mice survived, compared to 80% survival for normal mice (Correll et al., 1997). If MSP plays a role in the host response to endotoxemia, pro-MSP must be cleaved to biologically active MSP. Within 4 hr after i.v. administration of... 

The first diemokine, PF-4, was identified in 1977 [3] but it was not for almost a decade that other members of the family started to emerge, with the discovery of the proinflammatory chemokines IP-10 was identified in 1985 as a protein showing homology to PF4 [4], while IL-8 and the MI P-1 proteins were isolated in the late 1980s as active protein from tissues or culture supernatants. The neutrophil chemoattractant, IL-8, was purified from culture supernatant of stimulated blood monocytes [5] and the monocyte chemoattractants MIP-la and MIP-ip were purified from LPS-stimulated mouse macrophages [6]. The primary amino acid sequence of these chemokines rapidly led to the identification of the highly conserved four-cysteine motif described above and also allowed their classification into the two principal subclasses. The number of chemokines then grew rapidly... 

Based on numerous studies of the periprosthetic tissues, it is the activation of both recruited and resident cells that leads to the production and release of cytokines, chemokines, and growth factors by these cells. The acute response proinflammatory cytokines and chemokines produced by activated fibroblasts, macrophages, and mast cells include IL-la, 1L-1(3, lL-6, and TNF-a [24—27]. In most inflammatory reactions, the acute phase is typically a short-lived response, followed by the proinflammatory cytokine and chemokine release that perpetuates a chronic inflammatory response, such as lL-6, lL-8, and monocyte chemoattractant protein (MCP-1), which are also detected... 

---