Tags

Type your tag names separated by a space and hit enter

Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways.
J Immunol. 2010 Jun 15; 184(12):7134-43.JI

Abstract

Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as asthma, chronic obstructive pulmonary disease, and atopic dermatitis. Enhanced TSLP expression has been detected in asthmatic airways that correlated with both the expression of Th2-attracting chemokines and with disease severity. Although cumulative evidence suggests that human airway smooth muscle (HASM) cells can initiate or perpetuate the airway inflammation by secreting a variety of inflammatory cell products such as cytokines and chemokines, the role of TSLP in this pathway is not known. In the current study, we sought to investigate whether HASM cells express the TSLP receptor (TSLPR) and whether it is functional. We first demonstrated that primary HASM cells express the transcript and protein of both TSLPR subunits (TSLPR and IL-7Ralpha). Functionally, TSLPR-mediated HASM activation induced a significant increase in CXC (IL-8/CXCL8), CC (eotaxin-1/CCL11) chemokines, and proinflammatory cytokine IL-6 expression. Furthermore, using biochemical and genetic approaches, we found that TSLP-induced proinflammatory gene expression in HASM involved the transcriptional mechanisms, MAPKs (ERK1/2, p38, and JNK), and STAT3 activation. Finally, TSLPR immunoreactivity in bronchial sections from mild allergic asthmatics suggested the potential in vivo TSLP targeting of HASM. Altogether, our data suggest that the TSLPR-mediated HASM activation induces proinflammatory cytokine and chemokines release that may facilitate inflammatory immune cells recruitment in airways. In addition, it may be inferred that TSLPR is involved in the pathogenesis of allergic asthma through the activation of HASM cells by TSLP.

Authors+Show Affiliations

Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20483734

Citation

Shan, Lianyu, et al. "Thymic Stromal Lymphopoietin Receptor-mediated IL-6 and CC/CXC Chemokines Expression in Human Airway Smooth Muscle Cells: Role of MAPKs (ERK1/2, P38, and JNK) and STAT3 Pathways." Journal of Immunology (Baltimore, Md. : 1950), vol. 184, no. 12, 2010, pp. 7134-43.
Shan L, Redhu NS, Saleh A, et al. Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. J Immunol. 2010;184(12):7134-43.
Shan, L., Redhu, N. S., Saleh, A., Halayko, A. J., Chakir, J., & Gounni, A. S. (2010). Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. Journal of Immunology (Baltimore, Md. : 1950), 184(12), 7134-43. https://doi.org/10.4049/jimmunol.0902515
Shan L, et al. Thymic Stromal Lymphopoietin Receptor-mediated IL-6 and CC/CXC Chemokines Expression in Human Airway Smooth Muscle Cells: Role of MAPKs (ERK1/2, P38, and JNK) and STAT3 Pathways. J Immunol. 2010 Jun 15;184(12):7134-43. PubMed PMID: 20483734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. AU - Shan,Lianyu, AU - Redhu,Naresh Singh, AU - Saleh,Ali, AU - Halayko,Andrew J, AU - Chakir,Jamila, AU - Gounni,Abdelilah S, Y1 - 2010/05/14/ PY - 2010/5/21/entrez PY - 2010/5/21/pubmed PY - 2010/6/19/medline SP - 7134 EP - 43 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 184 IS - 12 N2 - Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as asthma, chronic obstructive pulmonary disease, and atopic dermatitis. Enhanced TSLP expression has been detected in asthmatic airways that correlated with both the expression of Th2-attracting chemokines and with disease severity. Although cumulative evidence suggests that human airway smooth muscle (HASM) cells can initiate or perpetuate the airway inflammation by secreting a variety of inflammatory cell products such as cytokines and chemokines, the role of TSLP in this pathway is not known. In the current study, we sought to investigate whether HASM cells express the TSLP receptor (TSLPR) and whether it is functional. We first demonstrated that primary HASM cells express the transcript and protein of both TSLPR subunits (TSLPR and IL-7Ralpha). Functionally, TSLPR-mediated HASM activation induced a significant increase in CXC (IL-8/CXCL8), CC (eotaxin-1/CCL11) chemokines, and proinflammatory cytokine IL-6 expression. Furthermore, using biochemical and genetic approaches, we found that TSLP-induced proinflammatory gene expression in HASM involved the transcriptional mechanisms, MAPKs (ERK1/2, p38, and JNK), and STAT3 activation. Finally, TSLPR immunoreactivity in bronchial sections from mild allergic asthmatics suggested the potential in vivo TSLP targeting of HASM. Altogether, our data suggest that the TSLPR-mediated HASM activation induces proinflammatory cytokine and chemokines release that may facilitate inflammatory immune cells recruitment in airways. In addition, it may be inferred that TSLPR is involved in the pathogenesis of allergic asthma through the activation of HASM cells by TSLP. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20483734/Thymic_stromal_lymphopoietin_receptor_mediated_IL_6_and_CC/CXC_chemokines_expression_in_human_airway_smooth_muscle_cells:_role_of_MAPKs__ERK1/2_p38_and_JNK__and_STAT3_pathways_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20483734 DB - PRIME DP - Unbound Medicine ER -