A new interferon, limitin, displays equivalent immunomodulatory and antitumor activities without myelosuppressive properties as compared with interferon-alpha.

Abstract:

OBJECTIVE:Limitin is a new member of type I interferon (IFN) identified with an expression cloning based on the growth suppression of a myelomonocytic leukemia cell line WEHI3. Although limitin uses the IFN-alpha/beta receptor, its signal transduction pathways to express the antiviral effects are different from those of IFN-alpha. To clarify the characteristics of limitin, we compared the biological activities of limitin, such as the antiviral, immunomodulatory, antitumor, and myelosuppressive effects, with IFN-alpha. MATERIALS AND METHODS:Limitin and IFN-alpha were titered with a cytopathic effect dye binding assay. Induction of MHC class I on a keratinocyte cell line PAM212 was estimated with flow cytometry. Induction of OVA-restricted cytotoxic T lymphocyte (CTL) activity was analyzed with 51Cr release assay. Antiproliferative effects were evaluated with 3H-thymidine incorporation assay using WEHI3 and a lymphoblast cell line L1210. Myelosuppresive effects were evaluated with colony assay. In vivo side effects were estimated after the injection of limitin or IFN-alpha. RESULTS:Limitin had relatively higher antiviral activity than IFN-alpha. Limitin induced the surface expression of MHC class I, the enhancement of CTL activity, and the growth inhibition of lymphohematopoietic cell lines as strong as IFN-alpha. Nevertheless, the treatment of mice with limitin showed neither myelosuppression nor fever that are common adverse effects of IFN-alpha. CONCLUSIONS:Strong immunomodulatory, antitumor, and antiviral effects with weak myelosuppressive and weak acute toxic effects of limitin indicate that it may be useful as a new therapeutic drug for virus-hepatitis and cancers.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Kawamoto S,Oritani K,Asakura E,Ishikawa J,Koyama M,Miyano K,Iwamoto M,Yasuda S,Nakakubo H,Hirayama F,Ishida N,Ujiie H,Masaie H,Tomiyama Y

doi

10.1016/j.exphem.2004.06.008

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

797-805

issue

9

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(04)00207-3

journal_volume

32

pub_type

杂志文章
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    doi:

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