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Extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 mitogen-activated protein kinase signaling and activation of activator protein 1 and nuclear factor kappaB transcription factors play central roles in interleukin-8 expression stimulated by monosodium urate monohydrate and calcium pyrophosphate crystals in monocytic cells.
Arthritis Rheum. 2000 May; 43(5):1145-55.AR

Abstract

OBJECTIVE

Monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals cause acute gout and pseudogout, respectively. Because acute gout and pseudogout appear to be dependent on interleukin-8 (IL-8)-induced neutrophil ingress, this study was undertaken to define and compare how MSU and CPPD crystals stimulate IL-8 messenger RNA (mRNA) expression in mononuclear phagocytes.

METHODS

MSU and CPPD crystal-induced mitogen-activated protein kinase (MAPK) signal transduction and IL-8 transcriptional activation were studied in human monocytic cells, using the THP-1 cell line.

RESULTS

MSU and CPPD crystals (0.5 mg/ml) induced activation of c-Jun N-terminal kinase, extracellular signal-regulated kinase 1 (ERK-1)/ERK-2, and p38 MAPK pathways in THP-1 cells. Activation of the ERK-1/ERK-2 pathway was essential for MSU and CPPD crystal-induced IL-8 mRNA expression, whereas the p38 pathway played a greater role in IL-8 mRNA expression in response to CPPD crystals in comparison with MSU crystals. Both crystals induced the binding of nuclear factor kappaB (NF-kappaB), including the NF-kappaB complex c-Rel/RelA, and activator protein 1 (AP-1, including N-terminal phosphorylated c-Jun) to the IL-8 promoter. Both crystals induced transcriptional activation of the IL-8 promoter, which was dependent on activation of c-Rel/RelA and AP-1. Activation of the NF-IL-6 transcription factor played a lesser role. Finally, crystal-induced IL-8 promoter activation was mediated by activation of the ERK-1/ERK-2 pathway, as demonstrated by transfection of dominant-negative raf-1.

CONCLUSION

These results indicate that ERK-1/ ERK-2 signaling and transcriptional activation through AP-1 and NF-kappaB are essential for the induction of IL-8 expression in mononuclear phagocytes in response to CPPD and MSU crystals.

Authors+Show Affiliations

Department of Veterans Affairs Medical Center, University of California, San Diego 92161, USA.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
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10817569

Citation

Liu, R, et al. "Extracellular Signal-regulated Kinase 1/extracellular Signal-regulated Kinase 2 Mitogen-activated Protein Kinase Signaling and Activation of Activator Protein 1 and Nuclear Factor kappaB Transcription Factors Play Central Roles in Interleukin-8 Expression Stimulated By Monosodium Urate Monohydrate and Calcium Pyrophosphate Crystals in Monocytic Cells." Arthritis and Rheumatism, vol. 43, no. 5, 2000, pp. 1145-55.
Liu R, O'Connell M, Johnson K, et al. Extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 mitogen-activated protein kinase signaling and activation of activator protein 1 and nuclear factor kappaB transcription factors play central roles in interleukin-8 expression stimulated by monosodium urate monohydrate and calcium pyrophosphate crystals in monocytic cells. Arthritis Rheum. 2000;43(5):1145-55.
Liu, R., O'Connell, M., Johnson, K., Pritzker, K., Mackman, N., & Terkeltaub, R. (2000). Extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 mitogen-activated protein kinase signaling and activation of activator protein 1 and nuclear factor kappaB transcription factors play central roles in interleukin-8 expression stimulated by monosodium urate monohydrate and calcium pyrophosphate crystals in monocytic cells. Arthritis and Rheumatism, 43(5), 1145-55.
Liu R, et al. Extracellular Signal-regulated Kinase 1/extracellular Signal-regulated Kinase 2 Mitogen-activated Protein Kinase Signaling and Activation of Activator Protein 1 and Nuclear Factor kappaB Transcription Factors Play Central Roles in Interleukin-8 Expression Stimulated By Monosodium Urate Monohydrate and Calcium Pyrophosphate Crystals in Monocytic Cells. Arthritis Rheum. 2000;43(5):1145-55. PubMed PMID: 10817569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 mitogen-activated protein kinase signaling and activation of activator protein 1 and nuclear factor kappaB transcription factors play central roles in interleukin-8 expression stimulated by monosodium urate monohydrate and calcium pyrophosphate crystals in monocytic cells. AU - Liu,R, AU - O'Connell,M, AU - Johnson,K, AU - Pritzker,K, AU - Mackman,N, AU - Terkeltaub,R, PY - 2000/5/19/pubmed PY - 2000/6/3/medline PY - 2000/5/19/entrez SP - 1145 EP - 55 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 43 IS - 5 N2 - OBJECTIVE: Monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals cause acute gout and pseudogout, respectively. Because acute gout and pseudogout appear to be dependent on interleukin-8 (IL-8)-induced neutrophil ingress, this study was undertaken to define and compare how MSU and CPPD crystals stimulate IL-8 messenger RNA (mRNA) expression in mononuclear phagocytes. METHODS: MSU and CPPD crystal-induced mitogen-activated protein kinase (MAPK) signal transduction and IL-8 transcriptional activation were studied in human monocytic cells, using the THP-1 cell line. RESULTS: MSU and CPPD crystals (0.5 mg/ml) induced activation of c-Jun N-terminal kinase, extracellular signal-regulated kinase 1 (ERK-1)/ERK-2, and p38 MAPK pathways in THP-1 cells. Activation of the ERK-1/ERK-2 pathway was essential for MSU and CPPD crystal-induced IL-8 mRNA expression, whereas the p38 pathway played a greater role in IL-8 mRNA expression in response to CPPD crystals in comparison with MSU crystals. Both crystals induced the binding of nuclear factor kappaB (NF-kappaB), including the NF-kappaB complex c-Rel/RelA, and activator protein 1 (AP-1, including N-terminal phosphorylated c-Jun) to the IL-8 promoter. Both crystals induced transcriptional activation of the IL-8 promoter, which was dependent on activation of c-Rel/RelA and AP-1. Activation of the NF-IL-6 transcription factor played a lesser role. Finally, crystal-induced IL-8 promoter activation was mediated by activation of the ERK-1/ERK-2 pathway, as demonstrated by transfection of dominant-negative raf-1. CONCLUSION: These results indicate that ERK-1/ ERK-2 signaling and transcriptional activation through AP-1 and NF-kappaB are essential for the induction of IL-8 expression in mononuclear phagocytes in response to CPPD and MSU crystals. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10817569/Extracellular_signal_regulated_kinase_1/extracellular_signal_regulated_kinase_2_mitogen_activated_protein_kinase_signaling_and_activation_of_activator_protein_1_and_nuclear_factor_kappaB_transcription_factors_play_central_roles_in_interleukin_8_expression_stimulated_by_monosodium_urate_monohydrate_and_calcium_pyrophosphate_crystals_in_monocytic_cells_ L2 - https://doi.org/10.1002/1529-0131(200005)43:5<1145::AID-ANR25>3.0.CO;2-T DB - PRIME DP - Unbound Medicine ER -