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Interleukin-13 down-regulates the expression of neutrophil-derived macrophage inflammatory protein-1 alpha
T M Ohta1, T Kasama, M Hanyuuda
1First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Objective And Design:
To determine whether interleukin-13 (IL-13) possesses anti-inflammatory properties with respect to polymorphonuclear neutrophils (PMNs). Effects of IL-13 on production of the chemokine, macrophage inflammatory protein-1 alpha (MIP-1alpha), by PMNs were analyzed.
Subjects:
Human peripheral blood PMNs obtained from healthy volunteers.
Methods:
PMNs were stimulated by lipopolysaccharide (LPS) and/or IL-13 for selected periods of time, and MIP-1alpha expression was assessed by ELISA and Northern blot analysis.
Results:
IL-13 suppressed expression and production of PMN-derived MIP-1alpha mRNA and protein in a dose- and time-dependent manner. Inhibition of protein synthesis caused significant enhancement of MIP-1alpha mRNA expression. The inhibitory activity of IL-13 was abrogated, however, in the presence of cycloheximide, suggesting that IL-13's effect was via synthesis of de novo repressor protein(s).
Conclusions:
PMN-derived chemokines are regulated by both proinflammatory and immunomodulatory cytokines. The coordinated production of these substances is likely to be important in the orchestration of inflammatory and immune responses.