QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 8, 2006, 26(6):1880-1887; doi:10.1523/JNEUROSCI.3696-05.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Min, K.-J. Articles by Joe, E.-h. Search for Related Content PubMed PubMed Citation Articles by Min, K.-J. Articles by Joe, E.-h.

 Previous Article

Cellular/Molecular
Astrocytes Induce Hemeoxygenase-1 Expression in Microglia: A Feasible Mechanism for Preventing Excessive Brain Inflammation

Kyoung-Jin Min,^1,2,3 Myung-soon Yang,^2,3 Seung-Up Kim,^1,3,5 Ilo Jou,^2,4 and Eun-hye Joe^1,2,3

¹Neuroscience Graduate Program, ²Department of Pharmacology, ³Brain Disease Research Center, and ⁴Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 442-721, Korea, and ⁵Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4E3

Correspondence should be addressed to Dr. Eun-hye Joe, san-5 Woncheon-dong Youngtong-gu, Suwon, Kyunggi-do 442-721, Korea. Email: ehjoe{at}ajou.ac.kr

Microglia are the major inflammatory cells in the brain, in which microglial inflammatory responses are modulated by interactions with other brain cells. Here, we show that astrocytes, the most abundant cells in the brain, can secrete one or more factors capable of modulating microglial activation by regulating the microglial levels of reactive oxygen species (ROS). Treatment of microglia with astrocyte culture-conditioned media (ACM) increased the expression level and activity of hemeoxygenase-1 (HO-1). ACM also induced nuclear translocation of the nuclear factor E2-related factor 2 transcription factor, increased the binding activity of the antioxidant response element (ARE), and enhanced HO-1 promoter activity in an ARE-dependent manner. Furthermore, treatment with ACM suppressed interferon- (IFN-)-induced ROS production, leading to reduced inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release. In agreement with these results, mimickers of HO-1 products, such as bilirubin, ferrous iron, and a carbon monoxide-releasing molecule, reduced IFN--induced iNOS expression and/or NO release. Finally, we found that the active component(s) in ACM was heat labile and smaller than 3 kDa. Together, these results suggest that astrocytes could cooperate with microglia to prevent excessive inflammatory responses in the brain by regulating microglial expression of HO-1 and production of ROS.

Key words: brain inflammation; hemeoxygenase-1; cell–cell interaction; microglia; astrocyte; reactive oxygen species

---

Received Sept. 1, 2005; revised Dec. 28, 2005; accepted Dec. 28, 2005.

Correspondence should be addressed to Dr. Eun-hye Joe, san-5 Woncheon-dong Youngtong-gu, Suwon, Kyunggi-do 442-721, Korea. Email: ehjoe{at}ajou.ac.kr

This article has been cited by other articles:

				N. G. Innamorato, A. I. Rojo, A. J. Garcia-Yague, M. Yamamoto, M. L. de Ceballos, and A. Cuadrado The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation J. Immunol., July 1, 2008; 181(1): 680 - 689. [Abstract] [Full Text] [PDF]

				M.-J. Wang, S.-Z. Lin, J.-S. Kuo, H.-Y. Huang, S.-F. Tzeng, C.-H. Liao, D.-C. Chen, and W.-F. Chen Urocortin Modulates Inflammatory Response and Neurotoxicity Induced by Microglial Activation J. Immunol., November 1, 2007; 179(9): 6204 - 6214. [Abstract] [Full Text] [PDF]

				T. L. Hagemann, J. X. Connor, and A. Messing Alexander Disease-Associated Glial Fibrillary Acidic Protein Mutations in Mice Induce Rosenthal Fiber Formation and a White Matter Stress Response J. Neurosci., October 25, 2006; 26(43): 11162 - 11173. [Abstract] [Full Text] [PDF]

				D. J. Myer, G. G. Gurkoff, S. M. Lee, D. A. Hovda, and M. V. Sofroniew Essential protective roles of reactive astrocytes in traumatic brain injury Brain, October 1, 2006; 129(10): 2761 - 2772. [Abstract] [Full Text] [PDF]

				A. Y. Shih, H. B. Fernandes, F. Y. Choi, M. G. Kozoriz, Y. Liu, P. Li, C. M. Cowan, and A. Klegeris Policing the Police: Astrocytes Modulate Microglial Activation J. Neurosci., April 12, 2006; 26(15): 3887 - 3888. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help