Jun B D, Krueger G G, Roberts L K
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City 84132.
J Invest Dermatol. 1989 Jul;93(1):33-9. doi: 10.1111/1523-1747.ep12277340.
Keratinocyte expression of class II antigens (HLA-DR, human; Ia, murine) is associated with certain cutaneous diseases, especially those marked by the infiltration of immune and inflammatory cells into the skin. It has been shown that interferon-gamma (IFN-gamma) is capable of inducing human keratinocytes to express HLA-DR. Similar results, however, have not been duplicated in murine systems. The purpose of this study was to determine whether IFN-gamma was capable of inducing murine keratinocyte expression of Ia in vivo in an experimental model in which epithelial cells in a variety of organs were shown to express Ia after the i.v. injection of IFN-gamma. Recombinant murine IFN-gamma was injected into BALB/c mice. Biopsies of skin and intestine were analyzed by indirect immunoperoxidase to identify Ia-expressing keratinocytes and mucosal cells, respectively. Interferon-gamma was administered as either: 1) a single s.c. injection, 2) multiple i.v. injections of increasing doses (10(3)-10(5) U/d) on 3 consecutive d, or 3) i.p. injections of 5 X 10(4) U/d or 5 X 10(5) U/d on 6 consecutive d. At all i.v. and i.p. injection doses, the intestinal villi mucosal cells were induced to express Ia. Keratinocyte expression of Ia, however, was observed only in animals that received the two higher i.p. doses. Procedures to augment Ia expression, e.g., combined treatment with pertussis toxin, dinitrofluorobenzene, tumor necrosis factor, and indomethacin, did not enhance the ability of IFN-gamma to induce keratinocyte expression of Ia. We conclude that: 1) high doses of IFN-gamma are required to induce murine keratinocyte Ia expression in vivo and 2) low doses of IFN-gamma, although capable of inducing intestinal mucosal cells to express Ia, do not induce keratinocyte Ia expression.
角质形成细胞II类抗原（人类为HLA - DR；小鼠为Ia）的表达与某些皮肤疾病相关，尤其是那些以免疫和炎性细胞浸润皮肤为特征的疾病。已经表明，γ干扰素（IFN - γ）能够诱导人类角质形成细胞表达HLA - DR。然而，类似的结果在小鼠系统中尚未得到重复验证。本研究的目的是在一个实验模型中确定IFN - γ是否能够在体内诱导小鼠角质形成细胞表达Ia，在该模型中，静脉注射IFN - γ后，多种器官的上皮细胞被证明可表达Ia。将重组小鼠IFN - γ注射到BALB/c小鼠体内。通过间接免疫过氧化物酶法分析皮肤和肠道活检组织，分别鉴定表达Ia的角质形成细胞和黏膜细胞。IFN - γ的给药方式如下：1）单次皮下注射；2）连续3天多次静脉注射递增剂量（10³ - 10⁵ U/d）；或3）连续6天腹腔注射5×10⁴ U/d或5×10⁵ U/d。在所有静脉注射和腹腔注射剂量下，肠绒毛黏膜细胞均被诱导表达Ia。然而，仅在接受两种较高腹腔注射剂量的动物中观察到角质形成细胞表达Ia。增强Ia表达的方法，例如与百日咳毒素、二硝基氟苯、肿瘤坏死因子和吲哚美辛联合治疗，并未增强IFN - γ诱导角质形成细胞表达Ia的能力。我们得出结论：1）在体内诱导小鼠角质形成细胞Ia表达需要高剂量的IFN - γ；2）低剂量的IFN - γ虽然能够诱导肠黏膜细胞表达Ia，但不能诱导角质形成细胞表达Ia。
