Cyclic AMP- and IL6-Signaling Cross Talk: Comodulation of Proliferation and Apoptosis in the 7TD1 B Cell Hybridoma

Irvin, Brenda J.; Hanson, Cassandra L.; Smith, Laurens H.; Daniels, Christopher K.

doi:10.1006/excr.2001.5157

Cited by 12 publications

(14 citation statements)

References 31 publications

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“…The cAMP/PKA pathway induces IL-6 production in different cell types (36,37), and AhR activation is able to induce IL-6 production by de-repressing its promoter in tumor cell lines (23). Accordingly, our findings revealed a close relationship between AhR stimulation, cAMP, and cAMP-dependent IL-6 production.…”

Section: Discussionsupporting

confidence: 59%

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Sibilano

Frossi

Calvaruso

et al. 2012

The Journal of Immunology

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The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.

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Section: Discussionsupporting

confidence: 59%

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Sibilano

Frossi

Calvaruso

et al. 2012

The Journal of Immunology

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“…35,36 Second, cAMP exerts cell type-specific effects. Although cAMP leads to IL-6 expression in stromal cells and during osteoclastogenesis, 30 in other cells cAMP inhibits IL-6-dependent proliferation, 37 and in macrophages inhibition of the immune response by prostaglandin E2 is mediated by Gas and cAMP. 15 Third, it has to be mentioned that not only activated or increased Gas but also deficient or decreased Gas can be associated with malformation of skeletal bone and reduced bone mass turnover.…”

Section: Discussionmentioning

confidence: 99%

Gender‐dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty

Bachmann

Hanenkamp

Kornacki

et al. 2008

Journal Orthopaedic Research

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The G-protein Gas is involved in the physiology and pathophysiology of bone. Especially, Gas is a key regulator of interleukin-6, which is a potent promoter of aseptic loosening. We hypothesized that the common single nucleotide polymorphism GNAS1 T393C could also affect time to aseptic loosening. Caucasian patients were genotyped for the GNAS1 T393C polymorphism. Time and median time to aseptic loosening were analyzed for dependency on GNAS1 genotypes. Time and median time were not significantly associated with genotypes. Additional analysis corrected for gender revealed, that the TT genotype was associated with significantly longer time (p ¼ 0.048) as well as median time ( p ¼ 0.022) to aseptic loosening in female patients. In contrast to the findings in females, male TT genotype carriers had significantly shorter time ( p ¼ 0.018) and median time ( p ¼ 0.023) to aseptic loosening. Compared with TT genotype carriers heterozygous patients had a 6.25-fold lower risk with a hazard ratio of 0.160 ( p ¼ 0.016) and male patients carrying the CC genotype had an 11-fold lower risk with a hazard ratio of 0.088 ( p ¼ 0.006) in multivariate analysis. The present study suggests a significant gender-dependent role of the T393C polymorphism in aseptic loosening. The apparently contradictory results in women and men and the finding that the GNAS1 T393C genotype is an independent factor for time to aseptic loosening in male patients assigned this polymorphism as an interesting target for further investigations in bone diseases. ß

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“…Parent 7TD1 cells are dependent on IL6 for proliferation and are sensitive to dexamethasone-induced apoptosis. In our previous studies, we demonstrated that cyclic AMP (cAMP)-and IL6-dependent signaling pathways can interact, modulating proliferation and apoptosis of 7TD1 cells [29]. The aim of our current study was to elucidate the role of IL6-signaling in the development of resistance to the apoptotic effects of dexamethasone.…”

Section: Introductionmentioning

confidence: 94%

“…As previously described [29], 7TD1 cells were grown in complete culture medium consisting of RPMI-1640 with glutamine (GIBCO, Invitrogen Corporation) and was supplemented by 2 g/l sodium bicarbonate, (Fisher Scientific), 20 mM Hepes (Sigma Aldrich, St.Louis), 1% (v/v) penicillin/streptomycin antibiotic, (CELL GRO), 50 lg/ml gentamycin (MP Biomedicals, Aurora), 10% (v/v) FBS (Atlanta Biologicals, Lawrenceville), and 50 mM 2-mercaptoethanol (Sigma Aldrich, St.Louis). The cells were cultured with 4 ng/ml recombinant human IL6 (Upstate Biotechnology, Lake Placid, NY).…”

Section: Cell Culturementioning

confidence: 99%

Apoptotic resistance exhibited by dexamethasone-resistant murine 7TD1 cells is controlled independently of interleukin-6 triggered signaling

et al. 2008

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Interleukin-6 (IL6)-mediated signaling is known to play a role in pathogenesis and resistance in several cancers like multiple myeloma (MM). In this report we used the IL6-dependent 7TD1 murine B-cell hybridoma as an in vitro model to study the interactions between IL6-signaling pathways and the development of dexamethasone resistance. Though in initial stages, 7TD1 cells grew IL6-dependent and were sensitive to dexamethasone-induced apoptosis, chronic exposure to dexamethasone led to a dexamethasone-resistant phenotype (7TD1-Dxm) that grew independent of exogenous IL6. While IL6-mediated JAK/ STAT3 and PI3K/AKT signaling was important for proliferation of both cell lines, as shown in proliferation assays using the respective pathway inhibitors, AG490 and LY294002, the resistant cells were insensitive to induction of apoptosis using the same. STAT3 was constitutively phosphorylated in resistant cells and inhibition of its dimerization induced apoptosis but did not alter their insensitivity to dexamethasone. Our results suggest a role of entities downstream of IL6-mediated JAK/STAT3 signaling in development of dexamethasone resistance by 7TD1-Dxm cells.

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Cyclic AMP- and IL6-Signaling Cross Talk: Comodulation of Proliferation and Apoptosis in the 7TD1 B Cell Hybridoma

Cited by 12 publications

References 31 publications

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

Gender‐dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty

Apoptotic resistance exhibited by dexamethasone-resistant murine 7TD1 cells is controlled independently of interleukin-6 triggered signaling

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