Immunomodulatory Potential of Thymulin–Zn2+ in the Alveolar Epithelium: Amelioration of Endotoxin-Induced Cytokine Release and Partial Amplification of a Cytoprotective IL-10-Sensitive Pathway

Haddad, John J.; Land, Stephen C.; Saadé, Nayef E.; Safieh‐Garabedian, Bared

doi:10.1006/bbrc.2000.3155

Cited by 26 publications

(21 citation statements)

References 25 publications

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“…IL-1 from mononuclear cells plays a role in the pathogenesis of diabetes by impairing insulin secretion (7,10,26,29,33,34,36,43). However, Thymulin selectively ameliorated endotoxin-induced release of IL-1β in the perinatal epithelial cells (15). Our result showed IL-1β mRNA expression was decreased slightly by FTS.…”

Section: Discussionmentioning

confidence: 55%

Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

Saitoh

Awaya

Sakudo

et al. 2004

Microbiology and Immunology

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The protective effect of synthetic serum thymic factor (FTS) nonapeptide on lipopolysaccharide (LPS)‐induced pancreatic cell damage in 10‐week‐old BALB/c male mice was investigated. Mice were divided into three groups. Group I was treated with LPS (10 μg/head; i.p.) (LPS‐treated mice). Group II was administered with FTS (50 μg/head; i.p.) 24 hr before treatment with LPS and complemented immediately before LPS injection with FTS (50 μg/head; i.p.) (FTS‐administered mice). Group III was only treated with the same volume of saline (control mice). Treatment of LPS in vivo resulted in the destruction of pancreatic acinar cells. In those cells, many apoptotic cells were detected by immunohistochemistry using an anti‐single stranded DNA antibody. Immunohistochemistry and reverse transcription‐polymerase chain reaction (RT‐PCR) revealed that LPS treatment also caused low or a lack of insulin expression in pancreatic islets. In contrast, morphological change was not seen and apoptotic cell death was suppressed in pancreatic cells of FTS‐administered mice. Moreover, insulin expression was normal in those mice. FTS administration enhanced expression of Bcl‐2 mRNA levels in pancreatic tissues and IL‐6 mRNA levels in splenocytes significantly compared with those of LPS treatment at 3 hr after LPS injection. These findings suggest that FTS prevents LPS‐induced cell damage via enhancing Bcl‐2 expression in the pancreas and systemic IL‐6 production.

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Section: Discussionmentioning

confidence: 55%

Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

Saitoh

Awaya

Sakudo

et al. 2004

Microbiology and Immunology

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“…We have previously shown that the immunomodulatory potential mediated by thymulin is exhibited by downregulating an inflammatory signal through the differential reduction of the secretion of proinflammatory cytokines, including IL-1, IL-6, and TNF- [8][9][10][11]16,34]. This selective inhibition is accompanied by upregulating an anti-inflammatory response mediated by IL-10 [11], consistent with a counter-inflammatory signaling loop amplified by thymulin [40].…”

Section: Discussionmentioning

confidence: 75%

“…The carboxymethyl cellulose (1% CMC in 150mM NaCl) was used as a carrier in which thymic hormones and peptide analogues were administered [11]. Animals were stereotaxically monitored for accurate injections of ET intracerebroventricularly (ICV), with minimal stress under mild anesthesia.…”

Section: Thymic Hormone Immunomodulatory Effect On Et-induced Nf-b Ementioning

confidence: 99%

“…The biological activity of thymulin is dependent on equimolar interaction with Zn 2+ , whose bioavailability affects cellular immune functions under physiological and pathophysiological conditions [6,7]. Moreover, it has been shown that thymulin is capable of modulating proinflammatory cytokines in vitro and in vivo [8,9,10], providing an evidence for a novel anti-inflammatory propensity [11].…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that the effects of thymulin in downregulating an inflammatory can synergistically downregulate a pro-inflammatory signal by reducing the release of inflammatory mediators and by acting as an antioxidant [22,23]. Of particular importance, Zn 2+ is required in mediating antioxidantdependent inhibition of the redox-sensitive NF-B, a transcription factor essential to the expression of proinflammatory genes encoding cytokines and other inflammatory mediators [11,[24][25][26][27][28][29][30][31][32]. In addition, a redoxresponsive mechanism involving Zn 2+ has been implicated in regulating the DNA-binding kinetics of NF-B in vitro [33].…”

Section: Introductionmentioning

confidence: 99%

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The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Haddad¹,

Hanbali²

2013

AJMBR

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The immunomodulatory activity of thymulin and related analogues in vivo is not well characterized in the CNS. We have previously provided evidence for an anti-inflammatory potential of thymulin in downregulating proinflammatory cytokines in a NF-B-dependent mechanism in vitro. Furthermore, we have shown that intracerebroventricular (ICV) treatment with thymulin in the hippocampus (HC) reduced the nuclear localization and activation of NF-B, an effect mediated by the IB-α/pIB-α pathway in vivo. ICV stereotaxic injection of endotoxin (ET) differentially upregulated the nuclear translocation /expression of NF-B 1 (p50), NF-B 2 (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the HC. Pretreatment with thymulin followed by ET exposure reduced the nuclear translocation of NF-B subunits. The anti-inflammatory effect of thymulin seems to be mediated via the IB- pathway since thymulin downregulated ET-induced phosphorylation of IB-. Stereotaxic pretreatment with synthetic peptide analogue of thymulin (PAT) reduced the nuclear translocation of NF-B subunits, an effect mediated by downregulating the phosphorylation of IB-. EMSA revealed dose-dependent inhibition of NF-B/DNA activation mediated by ICV ET. These results indicate that the anti-inflammatory effect of thymulin/PAT, mediated by IB-, is NF-B-dependent and involves the downregulation of the nuclear translocation of various NF-B subunits and their subcellular activation.

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Nuclear Factor-κB-Independent Regulation of Lipopolysaccharide-Mediated Interleukin-6 Biosynthesis

Haddad

Fahlman

2002

Biochemical and Biophysical Research Communications

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Immunomodulatory Potential of Thymulin–Zn2+ in the Alveolar Epithelium: Amelioration of Endotoxin-Induced Cytokine Release and Partial Amplification of a Cytoprotective IL-10-Sensitive Pathway

Cited by 26 publications

References 25 publications

Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α

Nuclear Factor-κB-Independent Regulation of Lipopolysaccharide-Mediated Interleukin-6 Biosynthesis

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Immunomodulatory Potential of Thymulin–Zn2+ in the Alveolar Epithelium: Amelioration of Endotoxin-Induced Cytokine Release and Partial Amplification of a Cytoprotective IL-10-Sensitive Pathway

Cited by 26 publications

References 25 publications

Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-&#954;B-Dependent and Involves the Downregulation of I&#954;B-&#945;

Nuclear Factor-κB-Independent Regulation of Lipopolysaccharide-Mediated Interleukin-6 Biosynthesis

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The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α