Molecular cloning and functional characterization of guinea pig IL-12.
IL-12 is a heterodimeric cytokine that plays a central role in cell-mediated immunity. We cloned complete cDNAs of guinea pig homologues of IL-12 p35 and p40 subunits, and compared their functional properties with human IL-12. Both p35 and p40 mRNA were constitutively expressed in the testis and peritoneal macrophages. On immunoblotting, anti-guinea pig p40 antibody detected the constitutive expression of p40 protein in the testis, while in macrophages it was induced in response to lipopolysaccharide. An unidentified 200-kDa macromolecule was also expressed in the testis. All recombinant hybrid heterodimer p70 (guinea pig p70, human p70 and two interspecies heterodimers) exerted proliferative activity toward concanavalin A-primed guinea pig and human lymphoblasts in a dose-dependent manner. A similar tendency was observed in IFN-gamma production in IL-2-treated human lymphocytes. All hybrid heterodimers also induced IFN-gamma mRNA from IL-2-treated guinea pig splenocytes. Thus, unlike the current concept that the p35 subunit determines the species incompatibility of IL-12 in humans and mice, p35 has marginal ability to define its species-specific functional expression between humans and guinea pigs. In addition, constitutive expression of IL-12 or related molecules in the testis indicated a potential role of this molecule in regulation of physiological or pathophysiological conditions in the reproductive system.
Shiratori
I
I
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
Matsumoto
M
M
Tsuji
S
S
Nomura
M
M
Toyoshima
K
K
Seya
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006168:Guinea Pigs; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013737:Testis / Q000276:immunology; D014018:Tissue Distribution
D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma