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Studies on mitogen-activated protein kinase signaling pathway in the alveolar macrophages of chronic bronchitis rats

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Abstract

Lipopolysaccharide (LPS), a potent stimulator of inflammatory responses in alveolar macrophages (AMs), activates several intracellular signaling pathways, including mitogen-activated protein kinases (MAPK). In the present study, we investigated the MAPK pathway in AMs of chronic bronchitis (CB) rats. CB was induced by endotracheal instillation of LPS followed by Bacillus Calmette Guerin injection through the caudal vein 1 week later. Specific inhibitors were used and protein phosphorylations were detected by Western blot. We found that Genistein (PTK inhibitor) could inhibit protein kinase C (PKC), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt or PKB) MAPK signaling pathway with different degrees, LY294002 (PI3K inhibitor) could not only inhibit phospho-PI3K/Akt expression, but also inhibit p38 and c-Jun NH2-terminal kinases (JNK) phosphorylation. Calphostin C (PKC inhibitor) could inhibit phospho-PKC expression and exerted significant effects on extracellular signal-regulated kinases (ERK) phosphorylation, however, it had no impact on p38 and JNK phosphorylation. These results demonstrated that the LPS mediated signaling pathway of MAPK in AMs of CB rats could be described as follows: PTK-PI3K-Akt-JNK/p38 or PTK-PI3K-PKC-ERK, and PI3K may have a negative regulation on the activation of downstream proteins.

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Abbreviations

AMs:

Alveolar macrophages

CB:

Chronic bronchitis

LPS:

Lipopolysaccharide

BCG:

Bacillus Calmette Guerin

MAPK:

Mitogen-activated protein kinases

PKC:

Protein kinase C

PKA:

Protein kinase A

ERK:

Extracellular signal-regulated kinases

JNK:

c-Jun NH2-terminal kinases

FBS:

Fetal bovine serum

CMC:

Carboxymethylcellulose

BALF:

Bronchoalveolar lavage fluid

PI3K:

Phosphatidylinositol-3 kinase

PTK:

Receptor tyrosine kinase

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Acknowledgments

This work was supported by the National Science Foundations of China (No. 30572355), Provincial Science Foundation of Anhui (No. 090413134), Outstanding Young Teachers Foundation in Higher Education Institution (No. 2009SQRZ049ZD).

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Authors and Affiliations

  1. School of Pharmacy, Anhui Medical University, Tunxi West Road, Hefei, 230032, Anhui, China

    Yan Huang, Xiao-Ming Meng, Guo-Lin Jiang, Ya-Ru Yang, Juan Liu, Xiong-Wen Lv & Jun Li

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Correspondence to Jun Li.

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Huang, Y., Meng, XM., Jiang, GL. et al. Studies on mitogen-activated protein kinase signaling pathway in the alveolar macrophages of chronic bronchitis rats. Mol Cell Biochem 400, 97–105 (2015). https://doi.org/10.1007/s11010-014-2266-1

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