Induction of proinflammatory cytokines and caspase-1 by leptin in monocyte/macrophages from holstein cows.
The proliferation of peripheral blood mononuclear cells (PBMC) containing both monocyte/macrophages and T lymphocytes increased after treatment with T-cell mitogen (concanavalin A: Con A). PBMC treated with either leptin alone or combination of leptin and ConA showed enhanced proliferative activity by 10-40%, compared with those treated with ConA alone. In contrast, isolated T lymphocytes treated with leptin and ConA showed lowered proliferative activity than the ConA-treated alone, indicating that leptin induced production of some cytokines from monocyte/macrophages, that subsequently resulted in enhancement of T lymphocytes proliferation in PBMC. Among the cytokines examined, monocyte/monocytes constitutively expressed interleukin (IL)-1beta, IL-12p35, IL-18 mRNA, and faintly expressed tumor necrosis factor (TNF)-alpha and IL-12p40 mRNA. Leptin treatment augmented the monocyte/macrophages mRNA expression of only TNF-alpha and IL-12p40 to comparable levels of cells treated with lipopolysaccharide (LPS). However, leptin treatment increased monocyte/macrophages production of IL-1beta as well as TNF-alpha, and induced the mRNA expression of caspase-1, which is shown to mediate the conversion of latent pro-IL-1beta and pro-IL-18 to active forms. These results suggest that leptin directly acts on monocyte/macrophages to produce factors that induce T lymphocytes proliferation such as IL-12p35/p40 complex through IL-12p40 induction and IL-1beta/IL-18 production through caspase-1 induction.
Ahmed
Mohamed
M
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Shaban
Zein
Z
Yamaji
Daisuke
D
Okamatsu-Ogura
Yuko
Y
Soliman
Mohamed
M
Abd Eldaim
Mabrouk
M
Ishioka
Katsumi
K
Makondo
Kennedy
K
Saito
Masayuki
M
Kimura
Kazuhiro
K
D000704:Analysis of Variance; D000818:Animals; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D020738:Leptin / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D016207:Cytokines; D017931:DNA Primers; D020738:Leptin; D003208:Concanavalin A; D020169:Caspases