Dataset Information

Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization.

ABSTRACT: Modulation of the cluster of differentiation-36 receptor (CD36) has proven promising for dampening pro-inflammatory macrophage signaling. For example, azapeptides (e.g., 1 and 2) bind CD36 selectively with high affinity, mitigate Toll-like receptor (TLR) agonist-induced overproduction of nitric oxide (NO), and reduce pro-inflammatory cytokine and chemokine production in macrophages. Moreover, semicarbazides 1 and 2 inhibit microvascular sprouting mediated through CD36 in the choroid explant. Seeking a selective CD36 modulator that mediated inflammation without influencing neovascularization, a set of azasulfurylpeptides (e.g., 3a?e) were synthesized in which the semicarbazide was replaced by an N-aminosulfamide residue using a novel solid-phase approach. Notably, azasulfurylpeptide 3c diminished selectively CD36-mediated TLR-2-triggered inflammatory response without affecting neovascularization. Subtle chemical modification at the peptide backbone from a carbonyl to a sulfuryl residue has had a selective effect on biological activity providing a valuable probe for studying CD36 chemical biology.

SUBMITTER: Turcotte S

PROVIDER: S-EPMC6315388 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization.

Turcotte Stéphane S Mellal Katia K Chingle Ramesh R Mulumba Mukandila M Omri Samy S Dif-Yaiche Lylia L Chemtob Sylvain S Ong Huy H Lubell William D WD

Biomedicines 20181022 4

Modulation of the cluster of differentiation-36 receptor (CD36) has proven promising for dampening pro-inflammatory macrophage signaling. For example, azapeptides (e.g., 1 and 2) bind CD36 selectively with high affinity, mitigate Toll-like receptor (TLR) agonist-induced overproduction of nitric oxide (NO), and reduce pro-inflammatory cytokine and chemokine production in macrophages. Moreover, semicarbazides 1 and 2 inhibit microvascular sprouting mediated through CD36 ...[more]

PMID: 30360354

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Project description:IntroductionIn this retrospective study, resting-state functional connectivity (FC) in patients with migraine was analyzed to identify potential pathological pain processing patterns and compared them to those in healthy controls (HCs). The FC patterns in patients between pre- and post-acupuncture sessions were also analyzed to determine how acupuncture affects neurological activity and pain perception during the migraine interictal period.MethodsIn total, 52 patients with migraine without aura (MwoA) and 60 HCs were recruited. Patients with migraine were given acupuncture treatment sessions for 4 weeks. As a primary observation, functional magnetic resonance images were obtained at the beginning and end of the sessions. HCs received no treatment and underwent one functional magnetic resonance imaging (fMRI) scan after enrollment. After the fMRI data were preprocessed, a region of interest (ROI)-to-ROI analysis was performed with predefined ROIs related to pain processing regions.ResultsThe first analysis showed significantly different FCs between patients with MwoA and HCs [false discovery rate corrected p-value (p-FDR) < 0.05]. The FCs were found to be mainly between the cingulate gyrus (CG) and the insular gyrus, the CG and the inferior parietal lobule (IPL), the CG and the superior frontal gyrus, and the middle frontal gyrus and the IPL. The second analysis indicated that acupuncture treatment partly restored the different FCs found in the first analysis (p-FDR < 0.05). Furthermore, subgroup analysis found different brain activity patterns in headache-intensity restored condition and headache-frequency restored condition. Lastly, the correlation analysis suggested a potential correlation between FCs and clinical symptoms (p < 0.05).ConclusionThis study suggests that pain processing is abnormal in migraine, with significantly abnormal FCs in the frontal, parietal, and limbic regions. This finding could be a typical pathological feature of migraine. Acupuncture has been identified to relieve headache symptoms in two ways: it restores the pain processing function and regulates pain perception.

Project description:AimTo solidify the involvement of Saa-related pathway in corneal neovascularization (CorNV). The pathogenesis of inflammatory CorNV is not fully understood yet, and our previous study implicated that serum amyloid A (Saa) 1 (Saa1) and Saa3 were among the genes up-regulated upon CorNV induction in mice.MethodsMicroarray data obtained during our profiling project on CorNV were analyzed for the genes encoding the four SAA family members (Saa1-4), six reported SAA receptors (formyl peptide receptor 2, Tlr2, Tlr4, Cd36, Scarb1, P2rx7) and seven matrix metallopeptidases (Mmp) 1a, 1b, 2, 3, 9, 10, 13 reportedly to be expressed upon SAA pathway activation. The baseline expression or changes of interested genes were further confirmed in animals with CorNV using molecular or histological methods. CorNV was induced in Balb/c and C57BL/6 mice by placing either three interrupted 10-0 sutures or a 2 mm filter paper soaked with sodium hydroxide in the central area of the cornea. At desired time points, the corneas were harvested for histology examination or for extraction of mRNA and protein. The mRNA levels of Saa1, Saa3, Fpr2, Mmp2 and Mmp3 in corneas were detected using quantitative reverse transcription-PCR, and SAA3 protein in tissues detected using immunohistochemistry or western blotting.ResultsMicroarray data analysis revealed that Saa1, Saa3, Fpr2, Mmp2, Mmp3 messengers were readily detected in normal corneas and significantly up-regulated upon CorNV induction. The changes of these five genes were confirmed with real-time PCR assay. On the contrary, other SAA members (Saa2, Saa4), other SAA receptors (Tlr2, Tlr4, Cd36, P2rx7, etc), or other Mmps (Mmp1a, Mmp1b, Mmp9, Mmp10, Mmp13) did not show consistent changes. Immunohistochemistry study and western blotting further confirmed the expression of SAA3 products in normal corneas as well as their up-regulation in corneas with CorNV.ConclusionSAA-FPR2 pathway composing genes were expressed in normal murine corneas and, upon inflammatory stimuli challenge to the corneas, their expressions were up-regulated, suggesting their roles in pathogenesis of CorNV. The potential usefulness of SAA-FPR2 targets in future management of CorNV-related diseases deserves investigation.

Dataset Information

Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization.

Publications

Azasulfurylpeptide Modulation of CD36-Mediated Inflammation Without Effect on Neovascularization.

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