6th International AIDS Conference San Francisco, California, USA — June 20-23, 1990

Int Conf AIDS 1990 Jun 20-23; 6:340 (abstract no. 1106)
da Cunha A, Fauci AS, Vitkovic L; NIAID, NIH, Bethesda, Maryland, USA

OBJECTIVE: Interleukin-1 (IL-1) is induced by HIV-1 in monocytes and is proliferative for astrocytes. Since IL-1 is also elevated in cerebrospinal fluid (CSF) of AIDS patients we investigated its effect on astrocytic production of transforming growth factor beta (TGFbeta), a potent chemoattractant for monocytes.

METHODS: Astrocytes derived from 1-day-old rat cerebral cortices were grown for 2 to 4 weeks in 95% pure primary cultures. TGFbeta was measured in total cellular RNA by Northern and slot blot hybridization with [32P]dCTP-labeled EcoR1 insert of TGFbeta-1 cDNA under high stringency followed by autoradiography and densitometry. TGFbeta protein was detected immunocytochemically with affinity-purified rabbit anti-TGFbeta antibody (R & D Systems) as previously described. B cell lymphoma (BJAB) and 13-phorbol-12-myristate acetate (PMA) - stimulated Jurkat T cells served as positive and non-stimulated Jurkat T cells as negative controls for immunocytochemistry.

RESULTS: Astrocytes grown from 4 to 50 days contained a 2.4 kb RNA which hybridized with the TGFbeta cDNA. No other size RNA hybridized with this probe. The expression of 2.4 kb RNA in astrocytes increased during the first 2 weeks and remained constant thereafter. TGFbeta-like immunoreactivity was present in only some astrocytes just as it was present in some, but not all, control cells. The level of TGFbeta protein in astrocytes was lower than in controls as judged by the intensity of staining. IL-1 (5 U/ml) increased TGFbeta mRNA in 6 hours by 2 to 3 fold. This increase was dose-dependent and specific in that tumor necrosis factor alpha, PMA, and lipopolysaccharide were ineffective.

CONCLUSION: A subpopulation of cortical astrocytes constitutively express TGFbeta and this expression is stimulated by IL-1. These results suggest that secretion of IL-1 by HIV-infected monocytes may stimulate production of astrocytic TGFbeta which in turn may lead to monocytic infiltration of brain parenchyma.

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