Tags

Type your tag names separated by a space and hit enter

Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: a possible mechanism for downregulation of osteoclastogenesis.
Biochem Biophys Res Commun. 2005 Apr 15; 329(3):839-45.BB

Abstract

Interleukin-4 (IL-4), an anti-inflammatory cytokine, has been shown to inhibit osteoclast differentiation. Therefore, this cytokine is considered to be a promising therapeutic applicant for bone-resorbing diseases such as rheumatoid arthritis (RA). Recently NFATc1, a transcription factor, has been shown to play critical roles in osteoclastogenesis. The aim of this study was to clarify the role of IL-4 on the intracellular signaling of NFATc1. A RAW264.7 monocyte/macrophage cell line and murine bone marrow precursors were differentiated into osteoclasts in the presence of receptor activator of nuclear factor kappaB ligand (RANKL) and/or macrophage colony-stimulating factor. Tartrate-resistant acid phosphatase (TRAP) staining and a pit assay using dentine were used for the identification of activated osteoclasts. The protein expression of IL-4 receptor, NFATc1, and c-Fos was determined by Western blot analysis. In addition, the gene expression of NFATc1 and c-Fos was determined by reverse transcription and polymerase chain reaction. The IL-4 receptor was constitutively expressed in RAW264.7 cells. RANKL induced osteoclast generation, as determined by TRAP staining and pit assay. IL-4 inhibited RANKL-induced osteoclastogenesis at low concentrations of 10ng/ml and more. Interestingly, IL-4 potently inhibited RANKL-induced expression of NFATc1 at mRNA level. Furthermore, IL-4 inhibited c-Fos expression, which is shown to be responsible for NFATc1 expression, in time- and dose-dependent manners. In addition, IL-4 inhibited the RANKL-induced expression of NFATc1 and c-Fos in murine bone marrow cells. Thus, we suggest that IL-4 may downregulate osteoclastogenesis in part through inhibition of the expression of transcription factors, NFATc1 and c-Fos. These findings provide new insight into development of new medication for osteoporosis and RA.

Authors+Show Affiliations

Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan.No affiliation info availableNo affiliation info availableNo 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

15752732

Citation

Kamel Mohamed, Saad Gad, et al. "Interleukin-4 Inhibits RANKL-induced Expression of NFATc1 and c-Fos: a Possible Mechanism for Downregulation of Osteoclastogenesis." Biochemical and Biophysical Research Communications, vol. 329, no. 3, 2005, pp. 839-45.
Kamel Mohamed SG, Sugiyama E, Shinoda K, et al. Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: a possible mechanism for downregulation of osteoclastogenesis. Biochem Biophys Res Commun. 2005;329(3):839-45.
Kamel Mohamed, S. G., Sugiyama, E., Shinoda, K., Hounoki, H., Taki, H., Maruyama, M., Miyahara, T., & Kobayashi, M. (2005). Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: a possible mechanism for downregulation of osteoclastogenesis. Biochemical and Biophysical Research Communications, 329(3), 839-45.
Kamel Mohamed SG, et al. Interleukin-4 Inhibits RANKL-induced Expression of NFATc1 and c-Fos: a Possible Mechanism for Downregulation of Osteoclastogenesis. Biochem Biophys Res Commun. 2005 Apr 15;329(3):839-45. PubMed PMID: 15752732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: a possible mechanism for downregulation of osteoclastogenesis. AU - Kamel Mohamed,Saad Gad, AU - Sugiyama,Eiji, AU - Shinoda,Kouichiro, AU - Hounoki,Hiroyuki, AU - Taki,Hirofumi, AU - Maruyama,Muneharu, AU - Miyahara,Tatsuro, AU - Kobayashi,Masashi, PY - 2005/02/01/received PY - 2005/3/9/pubmed PY - 2005/5/17/medline PY - 2005/3/9/entrez SP - 839 EP - 45 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 329 IS - 3 N2 - Interleukin-4 (IL-4), an anti-inflammatory cytokine, has been shown to inhibit osteoclast differentiation. Therefore, this cytokine is considered to be a promising therapeutic applicant for bone-resorbing diseases such as rheumatoid arthritis (RA). Recently NFATc1, a transcription factor, has been shown to play critical roles in osteoclastogenesis. The aim of this study was to clarify the role of IL-4 on the intracellular signaling of NFATc1. A RAW264.7 monocyte/macrophage cell line and murine bone marrow precursors were differentiated into osteoclasts in the presence of receptor activator of nuclear factor kappaB ligand (RANKL) and/or macrophage colony-stimulating factor. Tartrate-resistant acid phosphatase (TRAP) staining and a pit assay using dentine were used for the identification of activated osteoclasts. The protein expression of IL-4 receptor, NFATc1, and c-Fos was determined by Western blot analysis. In addition, the gene expression of NFATc1 and c-Fos was determined by reverse transcription and polymerase chain reaction. The IL-4 receptor was constitutively expressed in RAW264.7 cells. RANKL induced osteoclast generation, as determined by TRAP staining and pit assay. IL-4 inhibited RANKL-induced osteoclastogenesis at low concentrations of 10ng/ml and more. Interestingly, IL-4 potently inhibited RANKL-induced expression of NFATc1 at mRNA level. Furthermore, IL-4 inhibited c-Fos expression, which is shown to be responsible for NFATc1 expression, in time- and dose-dependent manners. In addition, IL-4 inhibited the RANKL-induced expression of NFATc1 and c-Fos in murine bone marrow cells. Thus, we suggest that IL-4 may downregulate osteoclastogenesis in part through inhibition of the expression of transcription factors, NFATc1 and c-Fos. These findings provide new insight into development of new medication for osteoporosis and RA. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/15752732/Interleukin_4_inhibits_RANKL_induced_expression_of_NFATc1_and_c_Fos:_a_possible_mechanism_for_downregulation_of_osteoclastogenesis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(05)00267-6 DB - PRIME DP - Unbound Medicine ER -