Transforming growth factor beta 1 prevents cytokine-mediated inhibitory effects and induction of nitric oxide synthase in the RINm5F insulin-containing beta-cell line

Mabley, Jon G.; Cunningham, James M.; John, Nerys; Matteo, Martha; Green, I.C.

doi:10.1677/joe.0.1550567

Cited by 13 publications

(6 citation statements)

References 39 publications

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“…TGF-␤ is a type 2-associated cytokine that is a potent suppressor of nitric oxide synthetase 2 expression in mouse M⌽s (12,13). At 5,000 ng of LPS/ml, TGF-␤ production was enhanced as the concentration of MAX increased ( Fig.…”

Section: Resultsmentioning

confidence: 97%

Immunomodulatory Effects of theLutzomyia longipalpisSalivary Gland Protein Maxadilan on Mouse Macrophages

et al. 2007

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Infection with Leishmania major is enhanced when the sand fly Lutzomyia longipalpis salivary peptide maxadilan (MAX) is injected along with the parasite. Here we determined the effect that MAX has on the secretion of cytokines and nitric oxide (NO) and on parasite survival in macrophages (M⌽s). The cytokines produced by M⌽s can enhance a type 1 response, which will increase NO and the killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody production that is ineffective against intracellular pathogens such as L. major. A mouse macrophage cell line (RAW 264.7) was stimulated with various concentrations of MAX and lipopolysaccharide (LPS), and the supernatants were collected after 1, 2, and 3 days. Supernatants were assayed for interleukin-12p70 (IL-12p70), IL-10, IL-6, transforming growth factor ␤ (TGF-␤), NO, and tumor necrosis factor alpha (TNF-␣). Our results indicate that the addition of MAX upregulates the cytokines associated with a type 2 response (IL-10, IL-6, and TGF-␤) but downregulates type 1 cytokines (IL-12p70 and TNF-␣) and NO. MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs), and the parasite load increased significantly. The enhanced parasite load correlated with decreased NO production by PECs that were stimulated with LPS and gamma interferon in the presence of MAX. The ability of MAX to foster a type 2 response, to enhance parasite survival, and to decrease NO argues that MAX may be crucial for the early survival of Leishmania in the vertebrate host, and therefore, MAX holds considerable promise as an antigenic component for a vaccine against Leishmania.

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Section: Resultsmentioning

confidence: 97%

Immunomodulatory Effects of theLutzomyia longipalpisSalivary Gland Protein Maxadilan on Mouse Macrophages

et al. 2007

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“…Thus, it is plausible that the absence of c-FLIP expression by mesenchymal cells within fibroblastic foci may be related to their low level of NF-kB activation. Furthermore, we speculate that this low level of NF-kB activation may be consequential to: (1) an absence (or sub-threshold presence) of appropriate cytokine or other receptor agonists capable of activating NF-kB within fibroblastic foci; and/or (2) the presence of inhibitory cytokines or molecules such as TGF-b, which antagonizes NF-kB activation by proinflammatory stimui (48,49) and is localized to subepithelial areas of fibrosis in IPF (50,51).…”

Section: Discussionmentioning

confidence: 99%

Compartmentalized Expression of c-FLIP in Lung Tissues of Patients with Idiopathic Pulmonary Fibrosis

Cha¹,

Groshong²,

Frankel³

et al. 2010

Am J Respir Cell Mol Biol

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Increased apoptosis of alveolar epithelial cells and impaired apoptosis of myofibroblasts have been linked to the pathogenesis of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). Fas, a death receptor of the TNF-receptor superfamily, has been implicated in apoptosis of both cell types, though the mechanisms are poorly understood. The goals of this study were: (1) to examine the localization of Fas-associated death-domain-like IL-1beta-converting enzyme inhibitory protein (c-FLIP), an NF-kappaB-dependent regulator of Fas-signaling, in lung tissues from IPF/UIP patients and control subjects; and (2) to compare c-FLIP expression with epithelial cell and myofibroblast apoptosis, proliferation, and NF-kappaB activation. c-FLIP expression was restricted to airway epithelial cells in control lung tissues. In contrast, in patients with IPF/UIP, c-FLIP was also expressed by alveolar epithelial cells in areas of injury and fibrosis, but was absent from myofibroblasts in fibroblastic foci and from alveolar epithelial cells in uninvolved areas of lung tissue. Quantification of apoptosis and proliferation revealed an absence of apoptotic or proliferating cells in fibroblastic foci and low levels of apoptosis and proliferation by alveolar epithelial cells. Quantification of NF-kappaB expression and nuclear translocation revealed strong staining and translocation in alveolar epithelial cells and weak staining and minimal nuclear translocation in myofibroblasts. These findings suggest that: (1) c-FLIP expression is induced in the abnormal alveolar epithelium of patients with IPF/UIP, (2) the resistance of myofibroblasts to apoptosis in patients with IPF/UIP occurs independently of c-FLIP expression, and (3) increased NF-kappaB activation and c-FLIP expression by the alveolar epithelium may be linked.

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“…After hydrolysis, the reaction was terminated by inactivating the enzyme at Cell Culture A rat insulinoma cell line (RINm5F) was purchased from American Type Culture Collection. RIN, clone 5F (RINm5F), is an insulinoma cell line derived from an NEDH rat islet cell tumor [34]. Cells were grown at 37 o C under a humidified, 5% CO 2 atmosphere in RPMI-1640 medium supplemented with 10% fetal bovine serum, 100 units/ml of penicillin, and 100 µg/ml of streptomycin, and the medium was changed every three days.…”

Section: Methodsmentioning

confidence: 99%

Protective Effect of Cyclo(His-Pro) on Streptozotocin-Induced Cytotoxicity and Apoptosis In Vitro

Koo

Suh²,

Soo

et al. 2011

J. Microbiol. Biotechnol.

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Cyclo(His-Pro) (CHP) is a naturally occurring, cyclic dipeptide structurally related to thyrotropin-releasing hormone (TRH). CHP was efficiently obtained from soybean meal by hydrolysis with flavourzyme and alcalase. In this study, the effects of CHP on streptozotocin (STZ)-induced β-cell dysfunction and apoptosis were investigated in rat insulinoma cells (RINm5F) secreting insulin. When the RINm5F cells were treated with 2 mM STZ, insulin secretion decreased to approximately 54% that of control cells. However, CHP treatment restored the insulin-secreting activity of RINm5F cells to approximately 71% that of the untreated control cells. Moreover, CHP significantly protected the cells from STZ-mediated cytotoxicity via reduction of nitric oxide (NO) production (2.3-fold) and lipid peroxidation (1.9-fold), which were induced by STZ. Moreover, CHP treatment also attenuated STZ-induced apoptotic events, such as activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation in RINm5F cells, indicating that CHP could protect the cells from apoptotic cell death induced by oxidative stress of STZ by increasing the expression of an anti-apoptotic protein, Bcl-2. These results suggest that CHP could be a candidate material for a protective and therapeutic agent against STZ-mediated cytotoxicity and apoptosis.

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Transforming growth factor beta 1 prevents cytokine-mediated inhibitory effects and induction of nitric oxide synthase in the RINm5F insulin-containing beta-cell line

Cited by 13 publications

References 39 publications

Immunomodulatory Effects of theLutzomyia longipalpisSalivary Gland Protein Maxadilan on Mouse Macrophages

Immunomodulatory Effects of theLutzomyia longipalpisSalivary Gland Protein Maxadilan on Mouse Macrophages

Compartmentalized Expression of c-FLIP in Lung Tissues of Patients with Idiopathic Pulmonary Fibrosis

Protective Effect of Cyclo(His-Pro) on Streptozotocin-Induced Cytotoxicity and Apoptosis In Vitro

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