Lack of phospholipase C-delta1 induces skin inflammation.
Phospholipase C (PLC) is a key enzyme in phosphoinositide signaling. We previously generated PLC-delta1 knockout (KO) mice and found that these mice showed remarkable hair loss caused by abnormalities in hair follicle structures. Here we show that the skin of PLC-delta1 KO mice displays typical inflammatory phenotypes, including increased dermal cellularity, leukocyte infiltration, and expression of pro-inflammatory cytokines. In addition, exogenously expressed PLC-delta1 attenuates lipopolysaccharide-induced expression of IL-1beta, a pro-inflammatory cytokine, in an enzymatic activity-dependent manner. Furthermore, suppression of skin inflammation by anti-inflammatory reagents cured the epidermal hyperplasia in PLC-delta1 KO mice. Taken together, these results indicate that lack of PLC-delta1 induces skin inflammation and that the epidermal hyperplasia in PLC-delta1 KO mice is caused by skin inflammation. Our results also suggest that PLC-delta1 regulates homeostasis of the immune system in skin.
Ichinohe
Manabu
M
Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, 192-0392 Tokyo, Japan.
Nakamura
Yoshikazu
Y
Sai
Kentaro
K
Nakahara
Masamichi
M
Yamaguchi
Hideki
H
Fukami
Kiyoko
K
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004890:Erythema / Q000276:immunology* / Q000473:pathology*; D007113:Immunity, Innate / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology; D007527:Isoenzymes / Q000172:deficiency* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054803:Phospholipase C delta; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D010738:Type C Phospholipases / Q000172:deficiency* / Q000276:immunology*
D016207:Cytokines; D007155:Immunologic Factors; D007527:Isoenzymes; D010738:Type C Phospholipases; D054803:Phospholipase C delta; C518025:Plcd1 protein, mouse