JOURNAL ARTICLE

TGF-beta/Smad signaling inhibits IFN-gamma and TNF-alpha-induced TARC (CCL17) production in HaCaT cells

Koji Sumiyoshi, Atsuhito Nakao, Yasuhiro Setoguchi, Ryoji Tsuboi, Ko Okumura, Hideoki Ogawa
Journal of Dermatological Science 2003, 31 (1): 53-8
12615364

BACKGROUND: A Th2 chemokine, thymus and activation regulated chemokine (TARC/CCL17), produced by keratinocytes, is implicated in the development of atopic dermatitis by recruiting CLA(+)CCR4(+) lymphocytes into lesional skin and its expression was induced by proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). However, it remains unknown how TARC expression is negatively regulated in keratinocytes.

OBJECTIVE: We sought to determine whether transforming growth factor-beta 1 (TGF-beta 1) regulated TARC expression in keratinocytes.

METHODS: The effect of TGF-beta 1 on mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in a human keratinocyte cell line, HaCaT cells, was evaluated by using RT-PCR and ELISA. Adenovector-mediated gene transfer was used to determine the effect of Smad proteins on TARC expression in HaCaT cells.

RESULTS: TGF-beta 1 inhibited mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in HaCaT cells. The inhibitory effect of TGF-beta 1 on the TARC expression was suppressed by overexpression of Smad7, a major inhibitory regulator of Smad pathway for transforming growth factor-beta (TGF-beta) signaling, but not by PD98059, an inhibitor for ERK/mitogen-activated protein kinase (MAPK) pathway. In addition, overexpression of Smad2 or Smad3, major signal transducing Smads, was sufficient to inhibite the IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells.

CONCLUSION: TGF-beta1 inhibited IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells via Smad2/3, suggesting that modulation of TGF-beta/Smad signaling pathway may be beneficial for the treatment of atopic dermatitis.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
12615364
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"