Interleukin-13 down-regulates the expression of neutrophil-derived macrophage inflammatory protein-1 alpha.
OBJECTIVE
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.


METHODS
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.
Ohta
T M
TM
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Kasama
T
T
Hanyuuda
M
M
Hatano
Y
Y
Kobayashi
K
K
Negishi
M
M
Ide
H
H
Adachi
M
M
D015152:Blotting, Northern; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003513:Cycloheximide / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004791:Enzyme Inhibitors; D018793:Interleukin-13; D016209:Interleukin-8; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003609:Dactinomycin; D003513:Cycloheximide; D012321:DNA-Directed RNA Polymerases