Interferon- (cid:103) Increases the Sensitivity of Islets of Langerhans for Inducible Nitric-oxide Synthase Expression Induced by Interleukin 1*
Interferon- (cid:103) Increases the Sensitivity of Islets of Langerhans for Inducible Nitric-oxide Synthase Expression Induced by Interleukin 1*
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干扰素 - (cid:103) 提高胰岛对白细胞介素 1* 诱导的诱导型一氧化氮合酶表达的敏感性
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通讯作者：
J. Białkowski
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作者：
Jarosław Rycaj;A. Obersztyn;Anita Morzyk;J. Białkowski
本研究的目的是评价干扰素-（cid：103）（IFN-（cid：103））单独和联合白细胞介素1（IL-1（cid：98））对胰岛诱导型一氧化氮合酶（iNOS）mRNA和蛋白表达、亚硝酸盐产生和胰岛素分泌的影响。用IL-1（cid：98）处理大鼠胰岛导致亚硝酸盐产生的浓度依赖性增加，在5单位/ml时最大。单独地，0.1单位/ml IL-1（cid：98）或150单位/ml大鼠IFN-γ（cid：103）不刺激大鼠胰岛的iNOS表达或亚硝酸盐产生;然而，在组合中，这些细胞因子诱导iNOS表达和亚硝酸盐产生至与5单位/ml IL-1（cid：98）的单独作用相似的水平。在胰岛素依赖型糖尿病期间被选择性破坏的胰岛（cid：98）细胞似乎是iNOS的胰岛细胞来源之一，因为150单位/ml大鼠IFN-（cid：103）和0.1单位/ml IL-1（cid：98）在通过荧光激活细胞分选纯化的原代（cid：98）细胞和大鼠胰岛素瘤细胞系RINm 5 F中诱导了类似的效应。通过大鼠胰岛响应于150单位/ml大鼠IFN-（cid：103）和0.1单位/ml IL-1（cid：98）（cid：98）的iNOS表达和亚硝酸盐产生来确定人胰岛是否以类似方式响应。在这项研究中，我们表明，IL-1（cid：98），在浓度低至1单位/ml（5.7 μ M），能够刺激高水平的亚硝酸盐的生产，由人胰岛在人IFN-（cid：103）（750单位/ml）的存在下。我们还表明，在存在75单位/ml人IFN-（cid：103）的情况下，仅需10单位/ml IL-1（cid：98）就可诱导亚硝酸盐产生水平增加2倍。这些结果表明IFN-（cid：103）以与IFN-（cid：103）对大鼠胰岛的作用相似的方式降低刺激人胰岛iNOS表达所需的IL-1（cid：98）的浓度.
The purpose of this study was to evaluate the effects of interferon- (cid:103) (IFN- (cid:103) ) alone and in combination with interleukin 1 (cid:98) (IL-1 (cid:98) ) on inducible nitric-oxide synthase (iNOS) mRNA and protein expression, nitrite produc- tion, and insulin secretion by islets of Langerhans. Treatment of rat islets with IL-1 (cid:98) results in a concentra-tion-dependent increase in the production of nitrite that is maximal at 5 units/ml. Individually, 0.1 unit/ml IL-1 (cid:98) or 150 units/ml rat IFN- (cid:103) do not stimulate iNOS expression or nitrite production by rat islets; however, in com- bination, these cytokines induce the expression of iNOS and the production of nitrite to levels similar in magni- tude to the individual effects of 5 units/ml IL-1 (cid:98) . The islet (cid:98) -cell, selectively destroyed during insulin-depend-ent diabetes mellitus, appears to be one islet cellular source of iNOS as 150 units/ml rat IFN- (cid:103) and 0.1 unit/ml IL-1 (cid:98) induced similar effects in primary (cid:98) -cells purified by fluorescence-activated cell sorting and in the rat in- sulinoma cell line, RINm5F. iNOS expression and nitrite production by rat islets in response to 150 units/ml rat IFN- (cid:103) and 0.1 unit/ml IL-1 (cid:98) (cid:98) to determine if human islets respond in a similar manner. In this study we show that IL-1 (cid:98) , at a concentration as low as 1 unit/ml (5.7 p M ), is able to stimulate high levels of nitrite production by human islets in the presence of human IFN- (cid:103) (750 units/ml). We also show that in the presence of 75 units/ml human IFN- (cid:103) , as little as 10 units/ml IL-1 (cid:98) is required to induce a 2-fold increase in the level of nitrite production. These results indicate that IFN- (cid:103) reduces the concentration of IL-1 (cid:98) required to stimulate iNOS expression by human islets in a manner similar to IFN- (cid:103) ’s effects on rat islets.