Regulation of tracheal antimicrobial peptide gene expression in airway epithelial cells of cattle.

Khaled Taha-Abdelaziz,Lesley Berghuis,Leanna Wyer,Jeff L Caswell,Mary Ellen Clark,Laura L Bassel

doi:10.1186/s13567-016-0329-x

Khaled Taha-Abdelaziz, Lesley Berghuis + Show 4 more

Open Access

https://doi.org/10.1186/s13567-016-0329-x

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Journal: Veterinary Research	Publication Date: Mar 17, 2016
Citations: 28	License type: cc-by

Affiliation: University of Guelph, Beni-Suef University

Abstract

β-defensins are an important element of the mucosal innate immune response against bacterial pathogens. Tracheal antimicrobial peptide (TAP) has microbicidal activity against the bacteria that cause bovine respiratory disease, and its expression in tracheal epithelial cells is upregulated by bacterial products including lipopolysaccharide (LPS, a TLR4 agonist), Pam3CSK4 (an agonist of Toll-like receptor 2/1), and interleukin (IL)-17A. The objectives of this study were to identify the signalling pathway by which LPS, Pam3CSK4 and IL-17A induce TAP gene expression, and to determine the effect of glucocorticoid as a model of stress on this epithelial innate immune response. In primary cultures of bovine tracheal epithelial cells (bTEC), LPS, Pam3CSK4 and IL-17A each stimulated TAP gene expression. This effect was abrogated by caffeic acid phenylester (CAPE), an inhibitor of NF-κB. Similarly, western analysis showed that LPS, Pam3CSK4 and IL-17A each induced translocation of NF-κB p65 from the cytoplasm to the nucleus, but pre-treatment with CAPE inhibited this response. Finally, pre-treatment of bTEC with the glucocorticoid dexamethasone abolished the stimulatory effect of LPS, Pam3CSK4 and IL-17A on upregulation of TAP gene expression. These findings indicate that NF-κB activation is necessary for induction of TAP gene expression by LPS (a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist), or IL-17A. Furthermore, this stimulatory response is inhibited by glucocorticoid, suggesting this as one mechanism by which stress increases the risk of bacterial pneumonia. These findings have implications for understanding the pathogenesis of stress-associated bacterial pneumonia, and for developing methods to stimulate innate immune responses in the respiratory tract of cattle.

Highlights

Tracheal antimicrobial peptide (TAP) is a β-defensin produced by airway epithelial cells that has direct bactericidal activity against bacterial pathogens including those that cause respiratory disease in cattle [1,2,3]
Role of NF‐κB and Jun N-terminal kinase (JNK) signalling in inducible TAP gene expression in bovine tracheal epithelial cells (bTEC) Treatment of bTEC with LPS, Pam3CSK4, or IL-17A resulted in significant induction of TAP gene expression compared to non-stimulated cells
In bTEC stimulated for 16 h with 1 μg/mL Pam3CSK4, NF-κB p65 was detected in both the nuclear and the cytoplasmic fractions, whereas NF-κB p65 was detected only in the cytoplasmic fractions in bTEC treated with 10 μM caffeic acid phenylester (CAPE) prior to stimulation with Pam3CSK4 (Figure 2B)

Summary

Introduction

Tracheal antimicrobial peptide (TAP) is a β-defensin produced by airway epithelial cells that has direct bactericidal activity against bacterial pathogens including those that cause respiratory disease in cattle [1,2,3]. Risk factors for bovine respiratory disease are widely recognized and include the stresses of weaning, transportation, castration and inclement weather conditions, as well as viral infections, all of which occur at the time calves are removed from their dams and enter feedlots. These predisposing factors interfere with innate immune responses, alter bacterial populations in the nasal cavity, and are associated with increased number of bacteria reaching the lung [6].

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