Stimulation of Airway Mucin Gene Expression by Interleukin (IL)-17 through IL-6 Paracrine/Autocrine Loop*

By Yin Chen, Philip Thai, Yuhua Zhao, Y. Ho, M. Desouza, Reen Wu. Journal of Biological Chemistry, 2003

609 citations recorded by the source corpus.

Mucus hypersecretion and persistent airway inflammation are common features of various airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. One key question is: does the associated airway inflammation in these diseases affect mucus production? If so, what is the underlying mechanism? It appears that increased mucus secretion results from increased mucin gene expression and is also frequently accompanied by an increased number of mucous cells (goblet cell hyperplasia/metaplasia) in the airway epithelium. Many studies on mucin gene expression have been directed toward Th2 cytokines such as interleukin (IL)-4, IL-9, and IL-13 because of their known pathophysiological role in allergic airway diseases such as asthma. However, the effect of these cytokines has not been definitely linked to their direct interaction with airway epithelial cells. In our study, we treated highly differentiated cultures of primary human tracheobronchial epithelial (TBE) cells with a panel of cytokines (interleukin-1α, 1β, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, and tumor necrosis factor α). We found that IL-6 and IL-17 could stimulate the mucin genes, MUC5B andMUC5AC. The Th2 cytokines IL-4, IL-9, and IL-13 did not stimulate MUC5AC or MUC5B in our experiments. A similar stimulation of MUC5B/Muc5b expression by IL-6 and IL-17 was demonstrated in primary monkey and mouse TBE cells. Further investigation of MUC5B expression demonstrated that IL-17's effect is at least partly mediated through IL-6 by a JAK2-dependent autocrine/paracrine loop. Finally, evidence is presented to show that both IL-6 and IL-17 mediate MUC5Bexpression through the ERK signaling pathway.

Subfields: Emergency Medical Services, Physiology, Small Animals

View Paper: https://www.semanticscholar.org/paper/94920a2cfc33b68bfbcd6e20761fdaa878c5a525

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Citations in the corpus

• Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. (2009, background): “…(Forlow et al., 2001; Ye et al., 2001b) and host defense against Klebsiella or Candida infections (Huang et al., 2004; Ye et al., 2001a), and it can also protect mucosal barrier functions by stimulating tight junction formation and mucin secretion (Chen et al., 2003; Kinugasa et al., 2000).”
• The biological functions of T helper 17 cell effector cytokines in inflammation. (2008, neutral): “In addition to CXC chemokines and G-CSF, IL-17A can increase mRNA and protein for the mucins, MUC5AC and MUC5B, in primary human bronchial epithelial cells in vitro (Chen et al., 2003).”
• IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. (2008, background): “In addition, Muc5 was undetectable in CECs.”
• Cilia and Mucociliary Clearance (2017, background): “CBF is temperature dependent (Clary-Meinesz et al. 1992; Sears et al. 2015); because there is an optimal temperature for the enzymatic hydrolysis of ATP by dynein, low temperatures decrease CBF.”
• Respiratory tract mucin genes and mucin glycoproteins in health and disease. (2006, background): “The TH2 cytokines IL-5 and IL-9 do not alter MUC5AC or MUC5B mRNA abundance in differentiated NHBE cells (45).”