Interleukin-6 production by murine B cells and B cell lines

Hobbs, Monte V.; McEvilly, Robert J.; Koch, Rick J.; Cardenas, Gustavo J.

doi:10.1016/0008-8749(91)90041-9

Cited by 23 publications

(7 citation statements)

References 34 publications

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“…WEHI-231 cells were treated with different concentrations of ingenol 3-angelate (1 nM-1000 nM) or PMA (0.3 nM-1000 nM), and the secreted IL-6 was determined by ELISA after 3-9 and 24 h incubation. WEHI-231 cells secrete a basal amount of IL-6 as reported previously (49), and the concentration of IL-6 in the supernatant increased with time (Fig. 6A).…”

Section: Resultssupporting

confidence: 84%

Characterization of the Interaction of Ingenol 3-Angelate with Protein Kinase C

et al. 2004

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Ingenol 3-angelate (I3A) is one of the active ingredients in Euphorbia peplus, which has been used in traditional medicine. Here, we report the initial characterization of I3A as a protein kinase C (PKC) ligand. I3A bound to PKC-␣ in the presence of phosphatidylserine with high affinity; however, under these assay conditions, little PKC isoform selectivity was observed. PKC isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells. In all of the three cell types, I3A inhibited cell proliferation with somewhat lower potency than did PMA. In intact CHO-K1 cells, I3A was able to translocate different green fluorescent protein-tagged PKC isoforms, visualized by confocal microscopy, with equal or higher potency than PMA. PKC-␦ in particular showed a different pattern of translocation in response to I3A and PMA. I3A induced a higher level of secretion of the inflammatory cytokine interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. I3A was unable to cause the same extent of association of the C1b domain of PKC-␦ with lipids, compared with PMA or the physiological regulator diacylglycerol, and was able to partially block the association induced by these agents, measured by surface plasmon resonance. The in vitro kinase activity of PKC-␣ induced by I3A was lower than that induced by PMA. The novel pattern of behavior of I3A makes it of great interest for further evaluation.

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Section: Resultssupporting

confidence: 84%

Characterization of the Interaction of Ingenol 3-Angelate with Protein Kinase C

et al. 2004

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“…Moreover, supernatants from LPS-stimulated cells contained biologically active IL-6 ( Fig. 9), consistent with reports demonstrating that LPS induces the production of IL-6 by murine B cells (11). Whether autocrine IL-6 contributes to LPS-induced differentiation cannot be concluded from our studies.…”

Section: Resultssupporting

confidence: 91%

“…9). This possibility was plausible, since IL-6 has been shown in some cases to act as an autocrine differentiation factor for human B cells (10,11,19,26,43), and in studies by Kishimoto and colleagues (17,18,44), IL-6 responsiveness VOL. 13,1993 on of B cells was frequently found to first require addition of growth factors, such as IL-5.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation.

Randall¹,

Lund²,

Brewer³

et al. 1993

Mol. Cell. Biol.

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Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We have identified a clonal, inducible B-cell lymphoma, CH12, that has this property. Both IL-5 and IL-6 can independently stimulate increases in steady-state levels of immunoglobulin and J-chain mRNA and proteins, and they both induce the differentiation of CH12 into high-rate antibody-secreting cells. Nevertheless, there are significant differences in the activities of these two lymphokines. First, while IL-6 acts only as a differentiation factor, IL-5 also augments the proliferation of CH12 cells. Second, the differentiation stimulated by IL-5 but not by is partially inhibited by IL4. Inhibition of IL-5-induced differentiation was not at the level of IL-5 receptor expression, since IL-4 did not inhibit IL-5-induced proliferation. Third, IL-5 but not IL-6 stimulated increased mouse mammary tumor proviral gene expression in CH12 cells. These results demonstrate that while both IL-5 and IL-6 may act as differentiation factors for B cells, they induce differentiation by using at least partially distinct molecular pathways. Our results also establish that B cells characteristic of a single stage of development can independently respond to Lymphokines are important in regulating different aspects of the activation, growth, and differentiation of B lymphocytes. Several lymphokines, including interleukin-5 (IL-5) and IL-6, appear to be involved in inducing murine B cells to secrete antibody. IL-5 was originally described as a factor that induced both growth and differentiation of B cells (reviewed in references 37 and 38). IL-5 enhances the growth of B cells stimulated with dextran sulfate, but not with anti-immunoglobulin (anti-Ig) and IL4, and induces growth and differentiation of certain B-cell lymphomas, including BCL1 (28,34,35,37) and CH12 (21,31,36). IL-6 was originally described as a human B-cell differentiation factor that acts on activated, but not resting, B cells and certain B-cell leukemias (reviewed in references 17 and 41). Unlike IL-5, IL-6 fails to stimulate B-cell growth (2, 18, 26), although it does act as a potent growth factor for certain myelomas and hybridomas (40,42).The relative requirements for IL-5 versus IL-6 as a B-cell differentiation factor are an enigma. In the mouse, IL-5 has been shown to be the essential lymphokine required for the differentiation of antibody-secreting B cells under certain experimental conditions (5,32). These data contrast with studies of humans, in which IL-6 has reproducibly been shown to be the necessary and sufficient differentiation factor for B cells (17,18,26). However, recent results from murine studies suggest that IL-5 and IL-6 may be required under distinct experimental conditions and that IL-5 may be the critical lymphokine only when B cel...

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“…B cells can produce immunoregulatory cytokines, such as IL-6 or IL-12, upon TLR4 or TLR9 ligation (Hobbs et al, 1991; Yi et al, 1996; Sun et al, 2005), but whether they can contribute to IIC production in vitro has not been investigated in detail. We find that LPS stimulates Rag1 −/− splenocytes to produce IL-6, and the addition of equal numbers of B cells results in a near doubling of IL-6 levels (Fig.…”

Section: Resultsmentioning

confidence: 99%