Induction of the chemokine beta peptides, MIP-1 alpha and MIP-1 beta, by lipopolysaccharide is differentially regulated by immunomodulatory cytokines gamma-IFN, IL-10, IL-4, and TGF-beta.
The macrophage occupies a central role in the host response to invasion, exerting its control over the developing inflammatory response largely through the elaboration of an assortment of endogenous mediators including many cytokines. The beta chemokine peptides, macrophage inflammatory protein [MIP]-1 alpha and MIP-1 beta, are two such effectors markedly up-regulated in macrophages following exposure to bacterial lipopolysaccharide (LPS). These highly homologous peptides, like the other members of the beta chemokine family, exhibit diverse but partially overlapping biological activity profiles, suggesting that the cellular participants and intensity of an inflammatory response may in part be regulated by selective expression of these chemokines. Studies reported here demonstrate that, in contrast to the "balanced" MIP-1 alpha/MIP-1 beta chemokine responses of LPS-stimulated macrophage cultures in vitro, circulating levels of MIP-1 beta are significantly higher than those of MIP-1 alpha following LPS administration in vivo. Further studies have revealed that several immunomodulatory cytokines known to be up-regulated in vivo as a consequence of exposure to an invasive stimulus (gamma-IFN, IL-10, IL-4, and transforming growth factor [TGF]-beta) down-regulated the LPS-induced release of MIP-1 alpha by macrophages in vitro, but spared the MIP-1 beta response. This altered pattern of secretion may explain, at least in part, the high circulating levels of MIP-1 beta relative to MIP-1 alpha observed in vivo in response to LPS challenge.
Sherry
B
B
Picower Institute for Medical Research, Manhasset, New York, USA. bsherry@picower.edu
Espinoza
M
M
Manogue
K R
KR
Cerami
A
A
D000818:Animals; D054407:Chemokine CCL4; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology* / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology
D054407:Chemokine CCL4; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma