RAPID COMMUNICATION: A synthetic peptide homologous to retroviral envelope protein down-regulates TNF-α and IFN-γ mRNA expression

Haraguchi, Soichi; Good, Robert A.; Cianciolo, George J.; Day, Noorbibi K.

doi:10.1002/jlb.52.4.469

Cited by 15 publications

(12 citation statements)

References 11 publications

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“…Cytokine mRNA levels were normalized on the basis of the level of human ,B-actin mRNA. As in prior reports using CKS-17 conjugated to BSA (18,22,25), MN21 consistently suppressed the stimulant-induced IL-2 and IFN-,y mRNA expression. This study further showed that MN21 inhibited the stimulant-induced expression of IL-12 p40 heavy chain mRNA.…”

supporting

confidence: 83%

“…We previously demonstrated that CKS-17 acts directly on monocytes/macrophages (24)(25)(26) and that CKS-17-treated monocytes inhibit staphylococcal enterotoxin-induced IFN-y production by T lymphocytes (24). Both IL-10 and IL-12 are produced predominantly by macrophages (31,35,40,42).…”

Section: Discussionmentioning

confidence: 99%

“…Cianciolo et al (12) synthesized a heptadecapeptide, termed CKS-17, representing the conserved domain within this region. This peptide is immunosuppressive in vitro and in vivo and inhibits production of mediators-e.g., interferon y (IFN-'y), interleukin (IL)-2, and tumor necrosis factor a (12,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

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Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein.

Haraguchi

Good

James-Yarish

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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supporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein.

Haraguchi

Good

James-Yarish

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…Of significance are observations by us and by others of the effect of this peptide on the immunoregulation of cytokines [17][18][19][20][21][22]. For example, CKS-17 strongly inhibited Th1 cytokines that were induced by a variety of stimulants such as staphylococcal enterotoxin, anti-CD3 plus anti-CD28, concanavalin A, and lipopolysaccharide.…”

Section: The Effects Of Cks-17 On Immunitymentioning

confidence: 85%

A potent immunosuppressive retroviral peptide: cytokine patterns and signaling pathways

2007

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A synthetic bioactive peptide composed of 17 amino acids (CKS-17) homologous to a highly conserved region of human and animal retroviral transmembrane envelope proteins induces not only significant immunoregulatory functions but also exhibits Th1-inhibiting properties, as described by its ability to suppress cell-mediated immunity and inhibit the production of interleukin (IL) 12, IL-2, gamma interferon, and tumor necrosis factor alpha, while enhancing IL-10. An important molecular mechanism responsible for the observed cytokine profiles by CKS-17 is provided by our findings demonstrating that this small peptide activates several intracellular signaling molecules, i.e., elevates intracellular cyclic adenosine monophosphate (cAMP) levels, and induces phosphorylation of extracellular signal-regulated kinase (ERK) 1 and 2, mitogen-activated protein kinase/ERK kinase (MEK), protein kinase D, Raf1, and phospholipase C gamma1 (PLCgamma1). The activation of ERK1/2 is via the PLCgamma1-protein kinase C-Raf1-MEK signaling cascade. The activation of both ERK1/2 and cAMP appears to be via a mechanism sensitive to AG879, a receptor tyrosine kinase inhibitor, but not to AG825, AG1296, or AG1478. Furthermore, phosphoinositide-3 kinase appears to mediate the CKS-17-induced activation of ERK1/2, but not of cAMP. A specific amino acid sequence as well as the dimerization of this peptide is required to confer these biological activities. The results obtained are compelling and reproducible. This highly conserved molecule may enable us to understand a basic mechanism(s) of intracellular signaling pathways, regulation of Th1/Th2 cytokines, immunosuppression, and immunologic tolerance.

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“…Furthermore, HERV envelope proteins like syncytin-2 have a highly conserved region called the immunosuppressive domain (ISD), which seems to be important for materno-fetal immune tolerance at the fetal sited cell layer of the placenta [17]. Additionally, the ISD peptide has immunosuppressive properties on human peripheral blood mononuclear cells and, for example, in mouse models of skin or peritoneal inflammation [18-20]. A diminished expression of syncytins is related to preeclampsia [21].…”

Section: Introductionmentioning

confidence: 99%

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

et al. 2018

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Background: Eight percent of the human genome consists of human endogenous retroviruses (HERV). These genetic elements are remnants of ancient retroviral germ-line infections. Altered HERV expression is associated with several chronic inflammatory diseases. A physiological role of the HERV-derived proteins syncytin-1 and -2 has been described for the integrity of the human placental cell layer in terms of maintaining feto-maternal tolerance. The aim of this project was to investigate HERV expression in Crohn’s disease (CD) with a further focus on syncytins in the gut. Material and Methods: Seventy-four ileal and colonic tissue samples of CD patients and healthy controls have been investigated for mRNA expression of major HERV groups by a comprehensive microarray screening. The most prominent differences have been validated by qRT-PCR. Immunohistochemistry (IHC), Western Blot (WB) and qRT-PCR were performed for syncytin-1 and -2. Results: HERV microarray screening revealed a distinct expression profile in ileal and colonic tissue, as well as differential expression in CD compared to healthy controls. qRT-PCR validated differential expression of at least 3 HERV-groups in CD. qRT-PCR, IHC and WB showed a tissue-dependent diminished epithelial expression of syncytins in inflamed CD. Conclusion: For the first time, HERV expression has been comprehensively studied in the gut. Between CD and healthy controls we could show a tissue dependent differential HERV expression profile. Notably, we could show that syncytin-1 and -2 are expressed in the epithelial layer in ileal and colonic tissue samples, whereas their diminished tissue-dependent expression in inflamed CD might modulate inflammatory processes at the gut barrier.

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RAPID COMMUNICATION: A synthetic peptide homologous to retroviral envelope protein down-regulates TNF-α and IFN-γ mRNA expression

Cited by 15 publications

References 11 publications

Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein.

Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein.

A potent immunosuppressive retroviral peptide: cytokine patterns and signaling pathways

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

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