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Regulation of TLR2 Expression and Function in Human Airway Epithelial Cells

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Abstract

Toll-like receptor (TLR1–6) mRNAs are expressed in normal human bronchial epithelial cells with higher basal levels of TLR3. TLR2 mRNA and plasma membrane protein expression was enhanced by pretreatment with Poly IC, a synthetic double-stranded RNA (dsRNA) known to activate TLR3. Poly IC also enhanced mRNA expression of adaptor molecules (MyD88 and TIRAP) and coreceptors (Dectin-1 and CD14) involved in TLR2 signaling. Additionally, mRNA expression of TLR3 and dsRNA-sensing proteins MDA5 and RIG-I increased following Poly IC treatment. In contrast, basal mRNA expression of TLR5 and TLR2 coreceptor CD36 was reduced by 77% and 62%, respectively. ELISA of apical and basolateral solutions from Poly IC-stimulated monolayers revealed significantly higher levels of IL-6 and GM-CSF compared with the TLR2 ligand PAM3CSK4. Pretreatment with anti-TLR2 blocking antibody inhibited the PAM3CSK4-induced increase in IL-6 secretion after Poly IC exposure. An increase in IL-6 secretion was also observed in cells stimulated with Alternaria extract after pretreatment with Poly IC. However, IL-6 secretion was not stimulated by zymosan or lipothechoic acid (LTA). These data demonstrated that upregulation of TLR2 following exposure to dsRNA enhances functional responses of the airway epithelium to certain (PAM3CSK4), but not all (zymosan, LTA) TLR2 ligands and that this is likely due to differences in coreceptor expression.

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Authors and Affiliations

  1. Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, 55108, USA

    Tamene Melkamu

  2. Departments of Immunology and Medicine, Division of Allergic Diseases, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Diane Squillace & Hirohito Kita

  3. Departments of Integrative Biology and Physiology and Animal Science, University of Minnesota, 495 Animal Science/Veterinary Medicine Building, 1988 Fitch Ave, St. Paul, MN, 55108, USA

    Scott M. O’Grady

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  1. Tamene Melkamu
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  2. Diane Squillace
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Correspondence to Scott M. O’Grady.

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Melkamu, T., Squillace, D., Kita, H. et al. Regulation of TLR2 Expression and Function in Human Airway Epithelial Cells. J Membrane Biol 229, 101–113 (2009). https://doi.org/10.1007/s00232-009-9175-3

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