Proinflammatory chemokine

Zhang N, Rogers TJ, Caterina M, Oppenheim JJ (2004) Proinflammatory chemokines, such as C-C chemokine hgand 3, desensitize mu-opioid receptors on dorsal root ganglia neurons. J Immunol 173 594-599... 

Intestinal mucosal cells also can activate mediators of inflammation. Intestinal epithelial cells express an array of cytokine receptors and produce a spectrum of immune mediators, suggesting that they play an integral role in mucosal innate and acquired immunity (Dwinell et al 1999). Consistent with those functions, human intestinal epithelial cells have been shown to upregu-late the expression and secretion of a variety of proinflammatory chemokines in response to infection with enteroinvasive pathogens or stimulation with proinflammatory cytokines. Epithelial cell-derived chemokines appear to act as mediators of intercellular communication between the epithelium and immune and inflammatory cells in the adjacent and underlying mucosa. 

It is a paradigm that a major role of proinflammatory chemokines is to mobilize innate and adaptive immune responses against infectious agents. However, some observations are difficult to reconcile with this paradigm. For example, interferons suppress the production of IL-8, and IL-8 in turn suppresses the antiviral activity of IFNa in association with a reduction... 

IL-10 Regulates chemokine mRNA expression Reduces proinflammatory chemokine expression such as IL-8 and MCP-1. May stimulate regulatory chemokines like HCC-4... 

The innate immune system relies on a series of cytokine cascades to achieve a rapid and massive neutrophil influx when needed. The first step of this cascade consists of the activation of sentinel cells, usually tissue macrophages or mast cells, by bacterial or fungal products. Macrophages then immediately release potent early response cytokines, such as lL-1 p andTNF-a, that act in a paracrine manner on nearby stromal cells and in an autocrine manner on the macrophages themselves, causing the release of massive amounts of proinflammatory chemokines. The local production of appropriate chemokines ultimately leads to the transendothelial migration of neutrophils from the peripheral blood. 

Rossi D, Vicari A, Hedrick J, Zlotnik A. Identification through bioinformatics of two new human proinflammatory chemokines. J Immunol 1997 158 1033-1036. 

Microarray analysis indicates that acute PVM infection is likewise accompanied by increased expression of mRNAs encoding interferon-beta and interferon response genes, as well as transcripts encoding proinflammatory chemokines CCL2, CCL5, CCL7 and CCLl 1. The contribution of these mediators to the cellular inflammatory response awaits formal immunologic and functional assessment. 

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... 

In conclusion, the mentioned studies suggest that proinflammatory chemokines can either sensitize or desensitize receptor functions on or directly activate peripheral NANC nerves. This cross-(de)sensitization between neuronal (anti)pain and chemokine receptors or direct activation of NANC nerves may contribute to the development of visceral pain observed in inflammatory bowel disease and irritable bowel syndrome. 

Waring JF, Liguori MJ, Luyendyk JP, Maddox JF, Ganey PE, Stachlewitz RF, North C, Blomme EA, Roth RA. Microarray analysis of lipopolysaccharide potentiation of trovafloxacin-induced liver injury in rats suggests a role for proinflammatory chemokines and neutrophils. J Pharmacol Exp Ther 2006 316(3) 1080—1087. 

Von Schillde, M.-A., Hormannsperger, G., Weiher, M., et al. (2012) Lactocepin secreted by Lactobacillus exerts antiinflammatory effects by selectively degrading proinflammatory chemokines. Cell Host Microbe 11, 387-396. 

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