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Pro‐inflammatory Role of Beta2‐Adrenoceptor Signaling in Human Airway Epithelial Cells in Response to IL‐13
Author(s) -
AlSawalha Nour Ahmad,
Pokkunuri Indira,
Bond Richard A.,
Knoll Brian J.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1166.5
Subject(s) - chemokine , mucin , eotaxin , eosinophil , signal transduction , mapk/erk pathway , mek inhibitor , inflammation , chemistry , monocyte , immunology , microbiology and biotechnology , endocrinology , biology , asthma , biochemistry
We have shown the role of β 2 ‐adrenoceptor (β 2 AR) signaling in inducing mucin content and inflammation in murine model of asthma. Our objective was to study the role of β 2 AR signaling in chemokine production and expression of a major airway mucin coding gene, MUC5AC, in normal human bronchial epithelial cells (NHBECs) in response to IL‐13. NHBECs were grown at air‐liquid interface (ALI) on transwell filters in the presence of 3μM epinephrine. Chemokine levels in subnatants were measured by multiplex ELISA on day 5 ALI. MUC5AC expression and phospho‐ERK1/2 were assessed by qRT‐PCR and immunoblotting on day 14 ALI. IL‐13 induced the release of eotaxin‐2, CXCL‐1 and MCP‐1 (eosinophil, monocyte, dendritic and memory T‐cell chemoattractants respectively) by 6.8, 3.8 and 6.9 fold respectively. Treatment with βAR antagonist nadolol reduced the levels of these chemokines to baseline. Nadolol and ICI‐118,551 (a β 2 AR selective antagonist) blocked IL‐13 induced MUC5AC expression, while CGP‐20712A (a β 1 AR selective antagonist) did not. U0126 (a MEK‐1/2 inhibitor) and H89 (a PKA inhibitor) reduced IL‐13 induced MUC5AC expression, but only U0126 reduced phospho‐ERK1/2 levels. Our data provides a strong evidence of the pro‐inflammatory role of β 2 AR signaling in mediating IL‐13 effect on human airway epithelium, and that ERK‐1/2 and PKA are components of the required β 2 AR signaling pathways. Supported by NIH 1R01A179236 to RAB