TGF-beta1-mediated regulation of thymus and activation-regulated chemokine (TARC/CCL17) synthesis and secretion by HaCaT cells co-stimulated with TNF-alpha and IFN-gamma.
Thymus and activation-regulated chemokine (TARC/CCL17) contributes not only to the recruitment of leukocytes, but is also involved in immune disorders, such as atopic dermatitis (AD) and bronchial asthma. We have previously reported that the levels of TARC were high in patients with AD and that lesional epidermis were strongly immunoreactive for TARC. In this paper, the effects of transforming growth factor (TGF)-beta(1) on the expression of TARC/CCL17 were examined in HaCaT cells, a human keratinocytes (KCs) cell line, co-stimulated with TNF-alpha and IFN-gamma. We found that TGF-beta(1) down-regulated the TARC synthesis and secretion of HaCaT cells co-stimulated with TNF-alpha and IFN-gamma in a dose-dependent manner. TGF-beta(1) at a concentration of 10ng/ml maximally inhibited this secretion. Northern blot analysis showed a similar inhibitory effect of TGF-beta(1) on TARC mRNA expression by HaCaT cells. The TGF-beta(1)-induced down-regulation of TARC/CCL17 in HaCaT cells suggests that TGF-beta(1) might regulate the TARC-related inflammatory processes, which may be important for understanding the pathogenesis of allergic diseases.
Zheng
Xueyi
X
Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan.
Nakamura
Koichiro
K
Tojo
Michiko
M
Oyama
Noritaka
N
Nishibu
Akiko
A
Satoh
Masataka
M
Kakinuma
Takashi
T
Wakugawa
Motoshi
M
Tamaki
Kunihiko
K
Kaneko
Fumio
F
D002460:Cell Line; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma