Immunology

Toskala, Elina

doi:10.1002/alr.21380

Cited by 13 publications

(10 citation statements)

References 50 publications

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“…This complex process encompasses a multistep reaction, involving recruitment of immune cells, vasodilatation, increased permeability and an extensive set of molecular mediators. Its goal is to eliminate the initial cause of cell injury, clear out necrotic cells damaged upon the insult and to initiate tissue repair (Toskala, 2014, Shalapour and Karin, 2015, Waisman et al , 2015). Both microbiologically-induced inflammation and sterile inflammation are characterized by the recruitment of neutrophils and macrophages as well as by the production of inflammatory cytokines and chemokines (Chen and Nuñez, 2010).…”

Section: Introductionmentioning

confidence: 99%

Connexins and their channels in inflammation

Willebrords

Yanguas

Maes

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

115

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Inflammation may be caused by a variety of factors and is a hallmark of a plethora of acute and chronic diseases. The purpose of inflammation is to eliminate the initial cell injury trigger, to clear out dead cells from damaged tissue and to initiate tissue regeneration. Despite the wealth of knowledge regarding the involvement of cellular communication in inflammation, studies on the role of connexin-based channels in this process have only begun to emerge in the last few years. In this paper, a state-of-the-art overview of the effects of inflammation on connexin signaling is provided. Vice versa, the involvement of connexins and their channels in inflammation will be discussed by relying on studies that use a variety of experimental tools, such as genetically modified animals, small interfering RNA and connexin-based channel blockers. A better understanding of the importance of connexin signaling in inflammation may open up towards clinical perspectives.

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Section: Introductionmentioning

confidence: 99%

Connexins and their channels in inflammation

Willebrords

Yanguas

Maes

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

115

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“…Other protective mechanisms associated with the nose are its immunological responsiveness and its high metabolic activity that includes cytochrome P450, glucuronyltransferases, carboxylesterases, glutathione S -transferase, aldehyde dehydrogenases, catalase, glutathione peroxidase, among others. 12,13…”

Section: Physiologymentioning

confidence: 99%

Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular

Emami

Tepper²,

Short

et al. 2017

Int J Toxicol

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As the need for nasal, ocular, spinal, and articular therapeutic compounds increases, toxicology assessments of drugs administered via these routes play an important role in human safety. This symposium outlined the local and systemic evaluation to support safety during the development of these drugs in nonclinical models with some case studies. Discussions included selection of appropriate species for the intended route; conducting nonclinical studies that closely mimic the intended use with adequate duration; functional assessment, if deemed necessary; evaluation of local tissues with special histological staining procedure; and evaluations of safety margins based on local and systemic toxicity.

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“…The occurrence and development of the animal immune system is a lengthy process, and it has been formed, developed and perfected gradually during long-term evolution and adaptation to biological development ( 1 , 2 ). The innate and adaptive immune systems act in concert to protect us from infectious agents and other harmful substances ( 1 , 2 ). As a state of temporary or permanent immune dysfunction, immunosuppression can make an organism more susceptible to infection, organ injury, and cancer due to damage to the immune system ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting the TLR2 Receptor With a Novel Thymopentin-Derived Peptide Modulates Immune Responses

Xin

Zhang

et al. 2021

Front. Immunol.

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The innate and adaptive immune systems act in concert to protect us from infectious agents and other harmful substances. As a state of temporary or permanent immune dysfunction, immunosuppression can make an organism more susceptible to infection, organ injury, and cancer due to damage to the immune system. It takes a long time to develop new immunomodulatory agents to prevent and treat immunosuppressive diseases, with slow progress. Toll-like receptor 2 (TLR2) agonists have been reported as potential immunomodulatory candidates due to their effective activation of immune responses. It has been demonstrated that thymopentin (TP5) could modulate immunity by binding to the TLR2 receptor. However, the fairly short half-life of TP5 greatly reduces its pharmacological potential for immunosuppression therapy. Although peptide cathelicidin 2 (CATH2) has a long half-life, it shows poor immunomodulatory activity and severe cytotoxicity, which seriously hampers its clinical development. Peptide hybridization is an effective approach for the design and engineering of novel functional peptides because hybrid peptides combine the advantages and benefits of various native peptides. In this study, to overcome all these challenges faced by the parental peptides, six hybrid peptides (CaTP, CbTP, CcTP, TPCa, TPCb, and TPCc) were designed by combining the full-length TP5 with different active fragments of CATH2. CbTP, the most potent TLR2 agonist among the six hybrid peptides, was effectively screened through in silico analysis and in vitro experiments. The CbTP peptide exhibited lower cytotoxicity than either CATH2 or TP5. Furthermore, the immunomodulatory effects of CbTP were confirmed in a CTX-immunosuppressed mouse model, which showed that CbTP has increased immunopotentiating activity and physiological stability compared to the parental peptides. CbTP successfully inhibited immunosuppression and weight loss, increased immune organ indices, and improved CD4+/CD8+ T lymphocyte subsets. In addition, CbTP significantly increased the production of the cytokine TNF-α and IL-6, and the immunoglobulins IgA, IgM, and IgG. The immunoenhancing effects of CbTP were attributed to its TLR2-binding activity, promoting the formation of the TLR2 cluster, the activation of the TLR2 receptor, and thus activation of the downstream MyD88-NF-кB signaling pathway.

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Immunology

Abstract: Today we have several immunomodulatory treatment options for patients with allergic airway diseases, such as subcutaneous and sublingual immunotherapy. An understanding of the basics of our immune system and its method of functions is key for using these therapies appropriately.

Cited by 13 publications

References 50 publications

Connexins and their channels in inflammation

Connexins and their channels in inflammation

Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular

Targeting the TLR2 Receptor With a Novel Thymopentin-Derived Peptide Modulates Immune Responses

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