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Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB.
J Heart Lung Transplant. 2005 Jul; 24(7):875-81.JH

Abstract

BACKGROUND

It has recently become clear that interleukin (IL)-8 plays a role in chronic neutrophilic inflammatory disorders, such as chronic rejection after lung transplantation. We have shown that IL-17--stimulated human airway smooth muscle cells (HASMC) are able to produce IL-8. The aim of this study was to determine whether p38 mitogen-activated protein kinase (MAPK), c-Jun amino-terminal kinase (JNK), p42/p44 extracellular signal-related kinase (ERK) and nuclear factor-kappaB (NF-kappaB) are involved in IL-17--induced IL-8 production in HASMC in vitro.

METHODS

We used human airway smooth muscle cells in culture. Western blotting was done to obtain data regarding activation of MAPK. Furthermore, we used specific inhibitors of MAPK to investigate their involvement in IL-17--induced IL-8 release, which was measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Western blotting clearly demonstrated that p38 MAPK, JNK and p42/p44 ERK were activated by IL-17 in HASMC. Using SB203580, a specific inhibitor of p38 MAPK, we detected a concentration-dependent inhibition of IL-17--induced IL-8 production with a maximal decrease of 63 +/- 5% (n=8, p<0.01). Curcumin, a specific inhibitor of JNK, also concentration-dependently reduced IL-17--induced IL-8 production, with a maximal decrease of 82+/-4% (n=8, p<0.01). U0126, a specific inhibitor of p42/p44 ERK, induced a maximal decrease of 84+/-5% (n=8, p<0.001). Pyrrolydine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, caused a 70+/-5% (n=8, p<0.01) decrease in IL-17--induced IL-8 production.

CONCLUSIONS

We found that IL-17 induces activation of p38MAPK, JNK and p42/p44ERK in HASMC. We also found that p38MAPK, JNK, p42/p44 ERK and NF-kappaB play an important role in IL-17--induced IL-8 production in HASMC in vitro. This may open up new opportunities for further treatment of this disease.

Authors+Show Affiliations

Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium.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

15982617

Citation

Wuyts, Wim A., et al. "Interleukin-17--induced Interleukin-8 Release in Human Airway Smooth Muscle Cells: Role for Mitogen-activated Kinases and Nuclear Factor-kappaB." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 24, no. 7, 2005, pp. 875-81.
Wuyts WA, Vanaudenaerde BM, Dupont LJ, et al. Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB. J Heart Lung Transplant. 2005;24(7):875-81.
Wuyts, W. A., Vanaudenaerde, B. M., Dupont, L. J., Van Raemdonck, D. E., Demedts, M. G., & Verleden, G. M. (2005). Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 24(7), 875-81.
Wuyts WA, et al. Interleukin-17--induced Interleukin-8 Release in Human Airway Smooth Muscle Cells: Role for Mitogen-activated Kinases and Nuclear Factor-kappaB. J Heart Lung Transplant. 2005;24(7):875-81. PubMed PMID: 15982617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB. AU - Wuyts,Wim A, AU - Vanaudenaerde,Bart M, AU - Dupont,Lieven J, AU - Van Raemdonck,Dirk E, AU - Demedts,Maurits G, AU - Verleden,Geert M, PY - 2004/01/20/received PY - 2004/04/19/revised PY - 2004/05/09/accepted PY - 2005/6/29/pubmed PY - 2006/7/14/medline PY - 2005/6/29/entrez SP - 875 EP - 81 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J Heart Lung Transplant VL - 24 IS - 7 N2 - BACKGROUND: It has recently become clear that interleukin (IL)-8 plays a role in chronic neutrophilic inflammatory disorders, such as chronic rejection after lung transplantation. We have shown that IL-17--stimulated human airway smooth muscle cells (HASMC) are able to produce IL-8. The aim of this study was to determine whether p38 mitogen-activated protein kinase (MAPK), c-Jun amino-terminal kinase (JNK), p42/p44 extracellular signal-related kinase (ERK) and nuclear factor-kappaB (NF-kappaB) are involved in IL-17--induced IL-8 production in HASMC in vitro. METHODS: We used human airway smooth muscle cells in culture. Western blotting was done to obtain data regarding activation of MAPK. Furthermore, we used specific inhibitors of MAPK to investigate their involvement in IL-17--induced IL-8 release, which was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Western blotting clearly demonstrated that p38 MAPK, JNK and p42/p44 ERK were activated by IL-17 in HASMC. Using SB203580, a specific inhibitor of p38 MAPK, we detected a concentration-dependent inhibition of IL-17--induced IL-8 production with a maximal decrease of 63 +/- 5% (n=8, p<0.01). Curcumin, a specific inhibitor of JNK, also concentration-dependently reduced IL-17--induced IL-8 production, with a maximal decrease of 82+/-4% (n=8, p<0.01). U0126, a specific inhibitor of p42/p44 ERK, induced a maximal decrease of 84+/-5% (n=8, p<0.001). Pyrrolydine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, caused a 70+/-5% (n=8, p<0.01) decrease in IL-17--induced IL-8 production. CONCLUSIONS: We found that IL-17 induces activation of p38MAPK, JNK and p42/p44ERK in HASMC. We also found that p38MAPK, JNK, p42/p44 ERK and NF-kappaB play an important role in IL-17--induced IL-8 production in HASMC in vitro. This may open up new opportunities for further treatment of this disease. SN - 1053-2498 UR - https://www.unboundmedicine.com/medline/citation/15982617/Interleukin_17__induced_interleukin_8_release_in_human_airway_smooth_muscle_cells:_role_for_mitogen_activated_kinases_and_nuclear_factor_kappaB_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(04)00278-5 DB - PRIME DP - Unbound Medicine ER -