Differential regulation of the expression of cytokine-induced neutrophil chemoattractant by mouse macrophages

The production of cytokine-induced neutrophil chemoattractant (CINC) by functionally diverse mouse bone-marrow-derived macrophages was determined. Studies showed that beta 1,3-glucan, IL-1 beta, TNF alpha and IFN gamma/TNF alpha induced expression and production of CINC in macrophages while neither IFN gamma nor TGF beta alone induced detectable CINC expression. Pretreatment or simultaneous treatment of macrophages with TGF beta resulted in suppression of CINC protein production. These studies demonstrate that IFN gamma and TNF alpha, found early during the inflammatory response, induce production of CINC, as well as induce macrophages into a cytocidal state that are capable of killing transformed cells, parasites and bacteria, and recruiting neutrophils. In contrast, TGF beta, found during reparative stages of the inflammatory response, suppressed production of CINC, while inducing the development of inflammatory macrophages that are capable of producing lysosomal enzymes, enhanced endocytosis and ingestion of particulate matter and function to scavenge debris, debride tissue and stimulate repair.