Immunomodulation by OK-432 and calcitonin gene-related peptide (CGRP) of nitric oxide synthase (NOS) and IL-1 beta gene expression and of HSV-1 pathogenicity in mouse skin Langerhans cells (LC).
The effect of HSV-1 infection in the epidermis on the expression of genes for nitric oxide synthase (NOS) and interleukin-1 beta (IL-1 beta), and the ability of OK-432 to alter this effect were studied. The genes for NOS and IL-1 beta are normally expressed in Langerhans cells as well as in keratinocytes. Neither administration of OK-432 nor infection with HSV-1 abrogates this gene expression. Calcitonin gene-related peptide (CGRP) can inhibit the ability of macrophages and Langerhans cells to act as antigen-presenting cells. The effect of treatment with CGRP on mouse footpads and subsequent infection with HSV-1 was studied and compared with the effects observed after treatment with a specific antagonist for CGRP. Viral DNA was detected in adrenal gland samples of mice treated with the virus only and of mice treated with either CGRP-(1-37) or its antagonist prior to injection of the virus. In spinal cord samples, viral DNA was only detected when mice were treated with the virus or the CGRP antagonist. CGRP-(1-37) at physiological concentrations does not enable HSV-1 injected into mouse footpad skin to reach tissues which are normally resistant.
Department of Molecular Virology, Hebrew University of Jerusalem, Israel.
C
C
Berkowitz-Balshayi
Y
Y
Becker
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics*; D015603:Keratinocytes / Q000378:metabolism; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D010844:Picibanil / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity*; D015996:Survival Rate
D000970:Antineoplastic Agents; D017931:DNA Primers; D004279:DNA, Viral; D007375:Interleukin-1; D010844:Picibanil; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide