Difficult problems strabismus

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• 作者：David A. Plager ; Bradley Black ; Joseph Calhoun ; David Guyton ; Andrea Molinari ; Alan Scott
• 关键词：Bronchial epithelial cells ; ERK1/2 ; GM-CSF ; MAP kinase ; Raf1
• 刊名：Journal of American Association for Pediatric Ophthalmology and Strabismus
• 出版年：2007
• 出版时间：February 2007
• 年：2007
• 卷：11
• 期：1
• 页码：107
• 全文大小：42 K

文摘

ML-1 (IL-17F) is a recently discovered cytokine, and its function remains elusive. GM-CSF is a crucial cytokine for the maturation of various cell types and regulates allergic airway inflammation.

Objective

The functional effect of ML-1 in the expression of GM-CSF was investigated.

Methods

The levels of gene and protein expression in normal human bronchial epithelial cells (NHBEs) in the presence or absence of various kinase inhibitors or, in some cases, of a Raf1 dominant-negative mutant were determined by RT-PCR and ELISA, respectively. Western blotting was performed to investigate kinase activation.

Results

The results showed first that ML-1 induces, in a time-dependent and dose-dependent manner, the gene and protein expression for GM-CSF NHBEs, which are associated with activation of Raf1 and MAP kinase kinase (MEK) kinases. Selective MEK inhibitors, PD98059 and U0126, and Raf1 kinase inhibitor I significantly inhibited ML-1–induced GM-CSF production. Furthermore, overexpression of Raf1 dominant-negative mutants inhibited IL-17F–induced GMCSF expression. The combination of PD98059 and Raf1 kinase inhibitor I completely blocked GM-CSF production, whereas 2 protein kinase C inhibitors, Ro-31-7549 and GF109203X, and a phosphatidylinositol 3-kinase inhibitor, LY294002, showed no inhibitory effect.

Conclusion

These findings suggest that ML-1 induces GM-CSF expression through the activation of the Raf1-MEK–extracellular signal-regulated kinase 1/2 pathway.