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KE-298 and its active metabolite KE-758 suppress nitric oxide production by murine macrophage cells and peritoneal cells from rats with adjuvant induced arthritis.
J Rheumatol 2001; 28(6):1229-37JR

Abstract

OBJECTIVE

To analyze the effects of KE-298 and KE-758 on lipopolysaccharide (LPS) induced nitric oxide (NO) production by the RAW264.7 murine macrophage cell line, and the effect of KE-758 on spontaneous NO production by peritoneal cells from rats with adjuvant induced arthritis.

METHODS

The amount of NO was determined using Griess reagents. The proteins for inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blot, then mRNA for interferon-beta (IFN)-beta, IFN regulatory factor-1 (IRF-1), and iNOS were detected by RT-PCR. Degradation of iNOS mRNA was analyzed using Northern blot. Nuclear factor-kappa B (NF-kappa B) in nuclear extracts was determined by EMSA. Adjuvant arthritis in rats was induced by inoculating heat killed Mycobacterium butyricum s.c. in the tail.

RESULTS

KE-298 and KE-758 suppressed NO production by LPS activated RAW264.7 cells by inhibiting iNOS gene expression. Neither LPS induced NF-kappa B activation nor degradation of iNOS mRNA was affected by KE-758 treatment. LPS induced IFN-beta and IRF-1 gene expression were markedly suppressed by KE-758. In rats with adjuvant induced arthritis, enhanced NO and iNOS production by cultured peritoneal cells and the development of arthritis were suppressed by KE-758.

CONCLUSION

KE-758 suppressed LPS induced iNOS gene expression by murine macrophage cells by inhibiting IFN-beta/IRF-1 expression. The potential of KE-758 to inhibit iNOS production might partly explain its efficacy on adjuvant induced arthritis in rats.

Authors+Show Affiliations

Department of Pharmacology, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Ohmiya, Saitama 330-8530, Japan. s15376@ccm.taisho.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11409114

Citation

Inoue, T, et al. "KE-298 and Its Active Metabolite KE-758 Suppress Nitric Oxide Production By Murine Macrophage Cells and Peritoneal Cells From Rats With Adjuvant Induced Arthritis." The Journal of Rheumatology, vol. 28, no. 6, 2001, pp. 1229-37.
Inoue T, Hamada Y, Takeshita K, et al. KE-298 and its active metabolite KE-758 suppress nitric oxide production by murine macrophage cells and peritoneal cells from rats with adjuvant induced arthritis. J Rheumatol. 2001;28(6):1229-37.
Inoue, T., Hamada, Y., Takeshita, K., Fukushima, K., & Higaki, M. (2001). KE-298 and its active metabolite KE-758 suppress nitric oxide production by murine macrophage cells and peritoneal cells from rats with adjuvant induced arthritis. The Journal of Rheumatology, 28(6), pp. 1229-37.
Inoue T, et al. KE-298 and Its Active Metabolite KE-758 Suppress Nitric Oxide Production By Murine Macrophage Cells and Peritoneal Cells From Rats With Adjuvant Induced Arthritis. J Rheumatol. 2001;28(6):1229-37. PubMed PMID: 11409114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - KE-298 and its active metabolite KE-758 suppress nitric oxide production by murine macrophage cells and peritoneal cells from rats with adjuvant induced arthritis. AU - Inoue,T, AU - Hamada,Y, AU - Takeshita,K, AU - Fukushima,K, AU - Higaki,M, PY - 2001/6/21/pubmed PY - 2002/1/5/medline PY - 2001/6/21/entrez SP - 1229 EP - 37 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 28 IS - 6 N2 - OBJECTIVE: To analyze the effects of KE-298 and KE-758 on lipopolysaccharide (LPS) induced nitric oxide (NO) production by the RAW264.7 murine macrophage cell line, and the effect of KE-758 on spontaneous NO production by peritoneal cells from rats with adjuvant induced arthritis. METHODS: The amount of NO was determined using Griess reagents. The proteins for inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blot, then mRNA for interferon-beta (IFN)-beta, IFN regulatory factor-1 (IRF-1), and iNOS were detected by RT-PCR. Degradation of iNOS mRNA was analyzed using Northern blot. Nuclear factor-kappa B (NF-kappa B) in nuclear extracts was determined by EMSA. Adjuvant arthritis in rats was induced by inoculating heat killed Mycobacterium butyricum s.c. in the tail. RESULTS: KE-298 and KE-758 suppressed NO production by LPS activated RAW264.7 cells by inhibiting iNOS gene expression. Neither LPS induced NF-kappa B activation nor degradation of iNOS mRNA was affected by KE-758 treatment. LPS induced IFN-beta and IRF-1 gene expression were markedly suppressed by KE-758. In rats with adjuvant induced arthritis, enhanced NO and iNOS production by cultured peritoneal cells and the development of arthritis were suppressed by KE-758. CONCLUSION: KE-758 suppressed LPS induced iNOS gene expression by murine macrophage cells by inhibiting IFN-beta/IRF-1 expression. The potential of KE-758 to inhibit iNOS production might partly explain its efficacy on adjuvant induced arthritis in rats. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/11409114/KE_298_and_its_active_metabolite_KE_758_suppress_nitric_oxide_production_by_murine_macrophage_cells_and_peritoneal_cells_from_rats_with_adjuvant_induced_arthritis_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=11409114 DB - PRIME DP - Unbound Medicine ER -