Astrocytes receptor, types

Unlike the effects of MOP activation, KOP stimulation typically has limited or opposing effects on astrocyte function. Eor example, KOP activation markedly reduces Tat-induced MCP-1 expression in human astrocytes (Sheng et al. 2003) or fails to affect CCL2 release by murine astrocytes (El-Hage et al. 2005). Morphine and Tat differently affect patterns of MOP and KOP expression in astrocytes, suggesting fundamental differences in the regulation of each receptor type (Turchan-Cholewo et al. 2008). The differences likely reflect the unique actions of MOP and KOP in astrocytes (Bohn et al. 2000 Belcheva et al. 2005), and are likely to be important for HlV-1 neuropathogenesis. 

While functional studies indicate that astrocytes possess TNF-Rs, the specific characterization of TNF-R 1 and TNF-R2 on human astrocytes under constitutive and activated conditions has not been well studied to date. The number of surface TNF-R 1 and TNF-R2 on human astrocytes has not been determined quantitatively there may be a differential expression of the two receptor types on astrocytes, as there is on epithelial and myeloid cells. Agonistic TNF-R antibodies, such as anti-TNF-Rl, mimic the effects of TNF by inducing normal human astrocytes to synthesize cytokines, such as IL-6 and monocyte chemoattractant protein 1, and to undergo growth modulation (Barna et al., 1993, 1994). Since anti-TNF-Rl but not anti-TNF-Rl antibodies induce an effect on normal human astrocytes, and only TNF-Rl transcripts are strongly detected in untreated fetal and adult astrocytes, it has been suggested that TNF-Rl is the predominant constitutive receptor type on human astrocytes (Barna et al., 1993 Tada et al., 1994). 

Astrocytes were purified and treated in the same manner as described in Table I, except that some cultures were stimulated for 5 and 7 days. After stimulation cell supernatants were removed, stored at -40°C, and then assayed for soluble tumor necrosis factor receptor type 1 (sTNF-Rl) and sTNF-R2 (Quantikine kits, R8cD Systems, Minneapolis, MN), tumor necrosis factor a (TNFa) (Quantikine HS, R cD Systems), and total nitric oxide (NOj) (in collaboration with L. J. Ignarro, UCLA, Los Angeles). Values are expressed as means SD. IFN, Interferon-y IL-1/3, interleukin-l 8. 

Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86 367-377 Liu Y, Liu H, Kim BO, Gattone VH, Li J, Nath A, Blum J, He JJ (2004) CD4-independent infection of astrocytes by human immunodeficiency virus type 1 requirement for the human mannose receptor. J Virol 78 4120 133... 

Other protein kinases may indirectly influence the activation of NF-kappap. For example, in contrast to the pro-inflammatory effects typically observed with activation of kinases, the elevation ofcAMP activates PKA and blocks transcription of iNOS mRNA [51,178, 229, 230]. Astrocytes contain a variety of NT receptors that are coupled to Gs-adenylate cyclase [231] and, either activation of P-adrenergic/dopamine receptors or employing agents that increase cAMP, such as forskolin (adenylate cyclase activator), PDE inhibitors [i.e. pentoxifylline], dibutyrl cAMP, or 8-bromo cAMP can attenuate lipopolysaccharide (LPS)/cytokine activated iNOS mRNA in microglia, astrocytes and a number of other cell types [51,176,177,178, 232-237]. In contrast, agents that suppress the intracellular concentration of cAM P such as H-89 and Rp-cAM P are pro-... 

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