Lymphokine mRNA expression by transplantable murine B lymphocytic malignancies. Tumor-derived IL-10 as a possible mechanism for modulating the anti-tumor response.
In vitro and in vivo expressions of cytokine mRNAs by four transplantable murine B lymphocytic malignancies designated A20, MOPC 315, 2PK-3, and RAW 8.1 were determined using sensitive reverse-transcribed (RT)-PCR. Despite significant differences in both the stage of B cell differentiation represented by each cell line and the method used to induce the original B lymphocytic tumors, IL-6 and IL-10 mRNAs were detected in each of the cultured cell lines. Whereas IL-2, IL-4, IL-5, and IL-12 mRNAs were not detected in cultured cells, expression of cytokine mRNAs in solid tumor tissue was quite different. RT-PCR of poly(A)+ RNA isolated from each of the four solid tumors demonstrated the presence of IL-4, IL-5, IL-6, IL-10, TGF-beta 1, and TNF-alpha mRNAs. There was a noticeable lack of significant IL-2 mRNA expression in any of the solid tumors. Using RT-PCR, it was clear that each of the malignant B lymphocytes expressed IL-6, IL-10, TGF-beta 1, and TNF-alpha, with limited expression of IL-4 and IL-5. To explore the mechanisms that might contribute to the lack of IL-2 mRNA in these solid tumors, quantitative competitive (QC)-RT-PCR was used to quantify expression of IL-10 mRNA. MOPC 315 tumor expressed the most IL-10 mRNA (23.2 pg/micrograms of poly(A)+ RNA), whereas 2PK-3, A20, and RAW 8.1 tumors expressed 7.4, 2.6, and 0.6 pg/micrograms of poly(A)+ RNA, respectively. Secretion of IL-10 into culture supernatants or into sera and ascitic fluid of tumor-bearing animals correlated with mRNA expression. This dysregulated IL-10 production in animals with B lymphocytic tumors suggested a mechanism that may account for the lack of IL-2 mRNA expression in solid tumors, and suggested a possible mechanism by which malignant B lymphocytes may limit cell-mediated antitumor responses.
Bost
K L
KL
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.
Bieligk
S C
SC
Jaffe
B M
BM
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10