The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin.

Abstract

Our knowledge of the induction of new molecules by IFN-gamma has led to the characterization of IP-10 and the preparation of a monospecific, polyclonal antibody. Using this reagent we have now examined inflammatory states occurring in human skin and used immunocytochemical staining for the expression of both Ia and IP-10 determinants. After evoking a delayed-type response to purified protein derivative of tuberculin (PPD), we noted the presence of IP-10 in dermal macrophages and endothelial cells. Intense staining of the basal layer of epidermal keratinocytes was prominent at 41 h, and by 1 wk the entire epidermis was staining. The comparison of the amount of IP-10 secreted by keratinocytes vs. macrophages, fibroblasts, and endothelial cells revealed that keratinocytes were by far the major producers of this molecule. The expression of Ia occurred in conjunction with IP-10. The injection of rIFN-gamma mimicked many of the features of the PPD response, including the expression of both Ia and IP-10 by epidermal keratinocytes. Coexpression was also found in the natural lesions of tuberculoid leprosy and cutaneous Leishmaniasis. However, it was absent in lepromatous leprosy, a state where activated T lymphocytes are not present. We suggest that the local production of IFN-gamma by T cells of the dermal infiltrate induces IP-10 formation in both the dermis and epidermis. IP-10 and Ia then serve as specific markers of immune IFN and its possible influence on effector cells of the cell mediated immune response.

IL-4 Enhances Keratinocyte Expression of CXCR3 Agonistic Chemokines

“…Also IL-17, a lymphokine expressed in ACD skin and released by nickel-specific CD4 ϩ T cells, was ineffective in regulating IP-10, Mig, and I-TAC, although keratinocytes express IL-17R, and IL-17 could modulate CC and CXC chemokine expression in keratinocytes (7,15). Other than in ACD, non-ELR chemokines have been shown to be expressed by keratinocytes in situ in other inflammatory skin diseases such as psoriasis and delayed-type hypersensitivity reactions as well as in cutaneous T cell lymphoma, suggesting an important contribution of these chemokines in the formation of the T cell infiltrate in different skin diseases (10,31,32).…”

“…In the skin environment, keratinocytes are considered the major source of IP-10 compared with endothelial cells, monocytes, and fibroblasts (10). The most efficient inducers of IP-10, Mig, and I-TAC synthesis in keratinocytes are IFN-␥ and TNF-␣ (4, 10, 11).…”

Intratumoral coinjection of adenoviral vectors expressing IL-2 and IL-12 results in enhanced frequency of regression of injected and untreated distal tumors

“…IFN-␥ is also known to be a potent upregulator of the chemokines IP-10 (interferon inducible protein 10) and MIG (monokine induced by gamma interferon). 42,43 Both of these molecules have been shown to be angiostatic [44][45][46] and thus increasing their expression would create a tumor microenvironment that is angiostatic resulting in inhibition of tumor growth.…”

Chemokine Expression Dynamics in Mycobacterial (Type-1) and Schistosomal (Type-2) Antigen-Elicited Pulmonary Granuloma Formation

“…26,32 Both MIG and IP-10 are chemotactic for NK cells and activated T lymphocytes in vitro, but not resting T cells, B cells, or neutrophils. [32][33][34][35][36] Moreover, IP-10 or MIG expression has been detected in a number of disease conditions with increased expression of IFN-␥ such as psoriasis, 18 tuberculoid leprosy, 19 sarcoidosis, 17 tuberculosis, 16 viral meningitis, 37 leishmaniasis, 14 toxoplasmosis, 38 ulcerative colitis, 15 and nephritic nephrosis. 39 Thus, IP-10 and MIG may provide good markers for Th1 or other interferon-dominant responses as suggested by Dixon and colleagues.…”