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Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF-κB-signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid.
Int Forum Allergy Rhinol. 2020 Jul 05 [Online ahead of print]IF

Abstract

BACKGROUND

Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa. Thymic stromal lymphopoietin (TSLP) is associated with T-helper 2 (Th2) response and induced by pathogen, allergen, toll-like receptor (TLR) ligands, and cytokines. Fibroblasts are known to be modulators of wound-healing, from inflammation to tissue remodeling. We examined effect of lipopolysaccharide (LPS) on TSLP production and the underlying mechanisms. We aimed to determine whether the effects of commonly used medications in CRS, namely corticosteroids, and macrolides, are related to LPS-induced TSLP in nasal fibroblasts.

METHODS

Fibroblasts were isolated from inferior turbinate tissues of CRS patients. TSLP and TLR4 expressions were determined by reverse transcript-polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunoassay, and immunofluorescence staining. Mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and nuclear factor-kappaB (NF-κB) phosphorylation was determined by Western blot and/or luciferase assay.

RESULTS

LPS increased TSLP expression in a dose- and time-dependent manner. LPS antagonist and corticosteroids inhibited TLR4 expression in LPS-stimulated fibroblasts. LPS-RS, macrolides, corticosteroids, and specific inhibitors suppressed LPS-induced alterations. Ex vivo culture showed similar results.

CONCLUSION

LPS induces TSLP production via the TLR4, MAPK, Akt, and NF-κB pathways. The effects of corticosteroids and macrolides are related to LPS-induced TSLP expression. We explored new treatment modalities targeting LPS-induced TSLP production that could replace the currently used corticosteroid and macrolides for treatment of CRS.

Authors+Show Affiliations

Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea.Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea. Medical Devices Clinical Trials Laboratory, Korea University College of Medicine, Seoul, South Korea.Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea. Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea. Medical Devices Clinical Trials Laboratory, Korea University College of Medicine, Seoul, South Korea.Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea. Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea. Medical Devices Clinical Trials Laboratory, Korea University College of Medicine, Seoul, South Korea. IVD Support Center, Korea University Guro Hospital, Seoul, South Korea.Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea. Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea. Medical Devices Clinical Trials Laboratory, Korea University College of Medicine, Seoul, South Korea.Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea. Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea. Medical Devices Clinical Trials Laboratory, Korea University College of Medicine, Seoul, South Korea. IVD Support Center, Korea University Guro Hospital, Seoul, South Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32623837

Citation

Kang, Ju-Hyung, et al. "Lipopolysaccharide Regulates Thymic Stromal Lymphopoietin Expression Via TLR4/MAPK/Akt/NF-κB-signaling Pathways in Nasal Fibroblasts: Differential Inhibitory Effects of Macrolide and Corticosteroid." International Forum of Allergy & Rhinology, 2020.
Kang JH, Yang HW, Park JH, et al. Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF-κB-signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid. Int Forum Allergy Rhinol. 2020.
Kang, J. H., Yang, H. W., Park, J. H., Shin, J. M., Kim, T. H., Lee, S. H., Lee, H. M., & Park, I. H. (2020). Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF-κB-signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid. International Forum of Allergy & Rhinology. https://doi.org/10.1002/alr.22641
Kang JH, et al. Lipopolysaccharide Regulates Thymic Stromal Lymphopoietin Expression Via TLR4/MAPK/Akt/NF-κB-signaling Pathways in Nasal Fibroblasts: Differential Inhibitory Effects of Macrolide and Corticosteroid. Int Forum Allergy Rhinol. 2020 Jul 5; PubMed PMID: 32623837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF-κB-signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid. AU - Kang,Ju-Hyung, AU - Yang,Hyun-Woo, AU - Park,Joo-Hoo, AU - Shin,Jae-Min, AU - Kim,Tae-Hoon, AU - Lee,Seung Hoon, AU - Lee,Heung-Man, AU - Park,Il-Ho, Y1 - 2020/07/05/ PY - 2020/03/09/received PY - 2020/06/01/revised PY - 2020/06/04/accepted PY - 2020/7/6/entrez PY - 2020/7/6/pubmed PY - 2020/7/6/medline KW - LPS KW - TSLP KW - chronic rhinosinusitis KW - ex vivo KW - nasal fibroblast KW - signaling pathway KW - steroid therapy KW - therapeutics JF - International forum of allergy & rhinology JO - Int Forum Allergy Rhinol N2 - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa. Thymic stromal lymphopoietin (TSLP) is associated with T-helper 2 (Th2) response and induced by pathogen, allergen, toll-like receptor (TLR) ligands, and cytokines. Fibroblasts are known to be modulators of wound-healing, from inflammation to tissue remodeling. We examined effect of lipopolysaccharide (LPS) on TSLP production and the underlying mechanisms. We aimed to determine whether the effects of commonly used medications in CRS, namely corticosteroids, and macrolides, are related to LPS-induced TSLP in nasal fibroblasts. METHODS: Fibroblasts were isolated from inferior turbinate tissues of CRS patients. TSLP and TLR4 expressions were determined by reverse transcript-polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunoassay, and immunofluorescence staining. Mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and nuclear factor-kappaB (NF-κB) phosphorylation was determined by Western blot and/or luciferase assay. RESULTS: LPS increased TSLP expression in a dose- and time-dependent manner. LPS antagonist and corticosteroids inhibited TLR4 expression in LPS-stimulated fibroblasts. LPS-RS, macrolides, corticosteroids, and specific inhibitors suppressed LPS-induced alterations. Ex vivo culture showed similar results. CONCLUSION: LPS induces TSLP production via the TLR4, MAPK, Akt, and NF-κB pathways. The effects of corticosteroids and macrolides are related to LPS-induced TSLP expression. We explored new treatment modalities targeting LPS-induced TSLP production that could replace the currently used corticosteroid and macrolides for treatment of CRS. SN - 2042-6984 UR - https://www.unboundmedicine.com/medline/citation/32623837/Lipopolysaccharide_regulates_thymic_stromal_lymphopoietin_expression_via_TLR4/MAPK/Akt/NF-κB-signaling_pathways_in_nasal_fibroblasts:_differential_inhibitory_effects_of_macrolide_and_corticosteroid L2 - https://doi.org/10.1002/alr.22641 DB - PRIME DP - Unbound Medicine ER -
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