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Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK signaling and reinforces inflammation in activated preadipocytes.
Am J Physiol Endocrinol Metab. 2010 May; 298(5):E930-40.AJ

Abstract

Increased expression and activity of the intracellular glucocorticoid-reactivating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) contribute to dysfunction of adipose tissue. Although the pathophysiological role of 11 beta-HSD1 in mature adipocytes has long been investigated, its potential role in preadipocytes still remains obscure. The present study demonstrates that the expression of 11 beta-HSD1 in preadipocyte-rich stromal vascular fraction (SVF) cells in fat depots from ob/ob and diet-induced obese mice was markedly elevated compared with lean control. In 3T3-L1 preadipocytes, the level of mRNA and reductase activity of 11 beta-HSD1 was augmented by TNF-alpha, IL-1 beta, and LPS, with a concomitant increase in inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), or IL-6 secretion. Pharmacological inhibition of 11 beta-HSD1 and RNA interference against 11 beta-HSD1 reduced the mRNA and protein levels of iNOS, MCP-1, and IL-6. In contrast, overexpression of 11 beta-HSD1 further augmented TNF-alpha-induced iNOS, IL-6, and MCP-1 expression. Moreover, 11 beta-HSD1 inhibitors attenuated TNF-alpha-induced phosphorylation of NF-kappaB p65 and p38-, JNK-, and ERK1/2-MAPK. Collectively, the present study provides novel evidence that inflammatory stimuli-induced 11 beta-HSD1 in activated preadipocytes intensifies NF-kappaB and MAPK signaling pathways and results in further induction of proinflammatory molecules. Not limited to 3T3-L1 preadipocytes, we also demonstrated that the notion was reproducible in the primary SVF cells from obese mice. These findings highlight an unexpected, proinflammatory role of reamplified glucocorticoids within preadipocytes in obese adipose tissue.

Authors+Show Affiliations

Division of Endocrinology and Metabolism, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54, Shogoin Kawaharacho, Sakyoku, Kyoto, 606-8507, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

19776225

Citation

Ishii-Yonemoto, Takako, et al. "Glucocorticoid Reamplification Within Cells Intensifies NF-kappaB and MAPK Signaling and Reinforces Inflammation in Activated Preadipocytes." American Journal of Physiology. Endocrinology and Metabolism, vol. 298, no. 5, 2010, pp. E930-40.
Ishii-Yonemoto T, Masuzaki H, Yasue S, et al. Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK signaling and reinforces inflammation in activated preadipocytes. Am J Physiol Endocrinol Metab. 2010;298(5):E930-40.
Ishii-Yonemoto, T., Masuzaki, H., Yasue, S., Okada, S., Kozuka, C., Tanaka, T., Noguchi, M., Tomita, T., Fujikura, J., Yamamoto, Y., Ebihara, K., Hosoda, K., & Nakao, K. (2010). Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK signaling and reinforces inflammation in activated preadipocytes. American Journal of Physiology. Endocrinology and Metabolism, 298(5), E930-40. https://doi.org/10.1152/ajpendo.00320.2009
Ishii-Yonemoto T, et al. Glucocorticoid Reamplification Within Cells Intensifies NF-kappaB and MAPK Signaling and Reinforces Inflammation in Activated Preadipocytes. Am J Physiol Endocrinol Metab. 2010;298(5):E930-40. PubMed PMID: 19776225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK signaling and reinforces inflammation in activated preadipocytes. AU - Ishii-Yonemoto,Takako, AU - Masuzaki,Hiroaki, AU - Yasue,Shintaro, AU - Okada,Sadanori, AU - Kozuka,Chisayo, AU - Tanaka,Tomohiro, AU - Noguchi,Michio, AU - Tomita,Tsutomu, AU - Fujikura,Junji, AU - Yamamoto,Yuji, AU - Ebihara,Ken, AU - Hosoda,Kiminori, AU - Nakao,Kazuwa, Y1 - 2009/09/23/ PY - 2009/9/25/entrez PY - 2009/9/25/pubmed PY - 2010/5/4/medline SP - E930 EP - 40 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 298 IS - 5 N2 - Increased expression and activity of the intracellular glucocorticoid-reactivating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) contribute to dysfunction of adipose tissue. Although the pathophysiological role of 11 beta-HSD1 in mature adipocytes has long been investigated, its potential role in preadipocytes still remains obscure. The present study demonstrates that the expression of 11 beta-HSD1 in preadipocyte-rich stromal vascular fraction (SVF) cells in fat depots from ob/ob and diet-induced obese mice was markedly elevated compared with lean control. In 3T3-L1 preadipocytes, the level of mRNA and reductase activity of 11 beta-HSD1 was augmented by TNF-alpha, IL-1 beta, and LPS, with a concomitant increase in inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), or IL-6 secretion. Pharmacological inhibition of 11 beta-HSD1 and RNA interference against 11 beta-HSD1 reduced the mRNA and protein levels of iNOS, MCP-1, and IL-6. In contrast, overexpression of 11 beta-HSD1 further augmented TNF-alpha-induced iNOS, IL-6, and MCP-1 expression. Moreover, 11 beta-HSD1 inhibitors attenuated TNF-alpha-induced phosphorylation of NF-kappaB p65 and p38-, JNK-, and ERK1/2-MAPK. Collectively, the present study provides novel evidence that inflammatory stimuli-induced 11 beta-HSD1 in activated preadipocytes intensifies NF-kappaB and MAPK signaling pathways and results in further induction of proinflammatory molecules. Not limited to 3T3-L1 preadipocytes, we also demonstrated that the notion was reproducible in the primary SVF cells from obese mice. These findings highlight an unexpected, proinflammatory role of reamplified glucocorticoids within preadipocytes in obese adipose tissue. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/19776225/Glucocorticoid_reamplification_within_cells_intensifies_NF_kappaB_and_MAPK_signaling_and_reinforces_inflammation_in_activated_preadipocytes_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00320.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -