Differential expression of mRNA encoding interleukin-12 p35 and p40 subunitsin situ

6533b872fe1ef96bd12d42c6

RESEARCH PRODUCT

Differential expression of mRNA encoding interleukin-12 p35 and p40 subunitsin situ

Eberhard Weihe Martin K.-h. Schäfer Tieno Germann Michael Bette Bernhard Fleischer Bernhard Fleischer Erwin Rüde Shen-chu Jin

subject

medicine.medical_treatment T cell Immunology Gene Expression Mice Nude Spleen Mice SCID In situ hybridization Biology Mice Gene expression medicine Animals Immunology and Allergy RNA Messenger In Situ Hybridization B cell Mice Inbred BALB C Messenger RNA Macrophages hemic and immune systems Interleukin-12 Molecular biology Mice Mutant Strains medicine.anatomical_structure Cytokine Interleukin 12 Spleen

description

Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the regulation of the immune response. For biological activity the expression of both subunits of IL-12, p35 and p40, is required. Moreover, in the mouse the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In the present study we have analyzed by in situ hybridization the expression of the p35 and p40 mRNA in the spleens of BALB/c and mutant (SCID, nude, beige) mice, unstimulated and after in vivo stimulation with lipopolysaccharide (LPS) and with staphylococcal enterotoxin B (SEB). In unstimulated spleens of BALB/c mice p35 and p40 mRNA were only detectable in a few strongly stained single cells, p35 mRNA was expressed in addition weakly in the B cell areas. After injection of LPS or SEB, p40 mRNA was strongly induced in the T cell areas all over the spleen, whereas expression of p35 mRNA and its distribution pattern did not change. Surprisingly, most of the mRNA for p35 and p40 was localized in different areas of the spleen and was apparently produced by different cells. In macrophage-depleted spleens the increased expression of p40 mRNA in response to LPS was reduced but still detectable, demonstrating that other cells besides macrophages can up-regulate IL-12 p40 mRNA. Nude mice showed a stronger expression of p35 mRNA, SCID mice lacked the weak p35 staining of the B cell areas but showed a strong basal expression of both p35 and p40 mRNA and a focal response to LPS. The pattern of IL-12 mRNA expression in beige mice was the same as in normal mice. These data demonstrate a spatial dissociation of expression of the two chains of IL-12 and are compatible with a regulatory role of the isolated IL-12 p40 chain in vivo. In addition, they indicate that the demonstration of mRNA for both chains of IL-12 in whole tissues or cell mixtures is not necessarily indicative of functional IL-12.

year	journal	country	edition	language
1994-10-01	European Journal of Immunology

https://doi.org/10.1002/eji.1830241026