China
Africa
Explore chapters and articles related to this topic
Psoriatic Arthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Elena Ciofoaia, Ana-Maria Orbai, Jason Liebowitz
A key challenge thus far in the treatment of PsA, and thus an area for potential future success, is the identification of novel autoantibodies that can be used to target disease pathogenesis (Yuan et al., 2019). In the coming years, it is our hope that novel therapeutic targets and novel biochemical markers may help with better management of PsA. Current treatment targets include the TNF/IL-23/IL-17A/IL-22 axis, which is a major contributor to the pathogenesis of psoriasis. However, several psoriasis autoantigens have recently been identified: cathelicidin (LL-37)-antimicrobial peptide, which is overexpressed in psoriatic epidermis as a reaction to skin injury/infection; ADAMTS-L5, which is expressed in melanocytes psoriatic target cells; lipid antigens generated by phospholipase A2 group IVD (PLA2G4D), which are expressed in psoriatic epidermis and eczematous lesions; and Keratin 17, which is expressed only in psoriatic lesions but not in normal skin. Moreover, levels of LL-37 and ADAMTS-L5 have been noted to be significantly elevated in patients with PsA, which suggests a potential role in the pathogenesis of PsA. However, these antibodies were also found in patients with systemic lupus erythematosus, indicating a possible lack of specificity for psoriasis, yet overall these antibodies may still prove useful as biomarkers for disease monitoring in patients with psoriasis or PsA (Ten Bergen et al., 2020).
Pharmaceuticals and Nutraceuticals from Fish and Their Activities
Published in Ramasamy Santhanam, Santhanam Ramesh, Subramanian Nivedhitha, Subbiah Balasundari, Pharmaceuticals and Nutraceuticals from Fish and Fish Wastes, 2022
Ramasamy Santhanam, Santhanam Ramesh, Subramanian Nivedhitha, Subbiah Balasundari
Antimicrobial activity: Its peptide, Cathelicidin 1, showed antimicrobial activity (Donati et al., 2011; https://www.uniprot.org/uniprot/J7GIU8). Antioxidant activity: The diethyl ether extracts of the skin and flesh of this species showed significant 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with 89.2% and 61.5%, respectively (Ekanayake et al., 2005).
Bactericidal/Permeability-Increasing Protein, p15s and Phospholipases A2, Endogenous Antibiotics in Host Defense Against Bacterial Infections
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Several isoforms of this cationic (pI > 11.0) 15 kDa protein from the secondary granules of rabbit PMN have been isolated and cloned (66,67). The structural features of the p15s have revealed that they belong to a recently recognized family of proteins found in pig, mouse, cow, rabbit, and human PMN that have been named cathelicidins (10,68,69). Common features include a conserved N-terminal proprotein and a highly variable C-terminal segment with antibacterial and LPS-binding activities (10,28,55,67,68,70). All members of this family contain four cysteines in the same positions of the pro-region. The two disulfide arrangements of the four cysteines in one of the cathelicidins have been identified (71). None of the holoproteins of the family members so far identified, except the p15s, possess antibacterial or other known bioactivity (10). Expression of the antibacterial activity of the other cathelicidin family members requires release of the C-terminal portion by proteolytic cleavage. In contrast, the full-length p15s are active without proteolysis as a condition for activity. Thus, the p15s apparently represent more distant members of the cathelicidin family. So far homologs of rabbit p15s have only been reported in mouse PMN (cDNA accession). The antibacterial activity of the p15s appears to be limited to gram-negative bacteria, probably reflecting, as in the case of BPI, specific interaction with the LPS component of the bacterial envelope. The p15s also inhibit the induction of host cell responses by LPS (55).
Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review
Published in Expert Review of Anti-infective Therapy, 2023
Ruby Benson, Mazhuvancherry Kesavan Unnikrishnan, Shilia Jacob Kurian, Saleena Ummer Velladath, Gabriel Sunil Rodrigues, Raghu Chandrashekar Hariharapura, Anju Muraleedharan, Dinesh Bangalore Venkateshiah, Barnini Banerjee, Chiranjay Mukhopadhyay, Aieshel Serafin Johnson, Murali Munisamy, Mahadev Rao, Benson Mathai Kochikuzhyil, Sonal Sekhar Miraj
While most of the published literature on the effects of vitamin D supplementation fail to evaluate its clinical effectiveness, understanding vitamin D’s role in the cathelicidin pathway as well as its pleiotropism in immunity would generate safe, simple, and cost-effective solutions for preventing and treating infections. Role of vitamin D in infections is explicit, especially because 25-dihydroxyvitamin D induces cathelicidin expression, in response to mycobacterial lipoprotein-induced activation of TLR2/1 on macrophages. Upon identifying a microbial infection, immune cells like macrophages change circulating vitamin D into 1,25-dihydroxy vitamin D, the active form that directly induces cathelicidin peptide, which functions as a signaling molecule to regulate immune activity. Since the discovery of 1,25-dihydroxy vitamin D-regulated cathelicidin expression, some in vivo antimicrobial functions of cathelicidin in humans are emerging. A recent study has shown how the vitamin D-induced cathelicidin influences immune cooperation between innate and adaptive immunity, inflammation, and autophagy pathway. In a study, vitamin D supplementation increased antimicrobial activity in ASL and abolished an antibody that inhibited anti-microbial activity. Yet another study found that cathelicidin is effective against Streptococcus mutans, a significant component of plaque that causes dental caries. To a fair extent, these studies provide evidence to the beneficial role of vitamin D-induced cathelicidin pathway in managing the infectious disease. Epidemiological studies in this area definitely merit further investigation.
Efficacy and safety of vitamin D in tuberculosis patients: a systematic review and meta-analysis
Published in Expert Review of Anti-infective Therapy, 2022
Jagdish Prasad Goyal, Surjit Singh, Ramakishan Bishnoi, Pankaj Bhardwaj, Rimple Jeet Kaur, Sameer Dhingra, Dharmveer Yadav, Siddhartha Dutta, Jaykaran Charan
Vitamin D can be considered as potential intervention for the treatment of TB. Vitamin D stimulates bactericidal activity of human macrophages against Mycobacterium tuberculosis (MTB) by inducing an antimicrobial peptide cathelicidin that leads to the killing of the MTB located inside the cells. It has been hypothesized that, in the vitamin D-deficient state, this natural protective mechanism gets deranged and that leads to increase in the susceptibility for tubercular infections [3,4]. Vitamin D binds to its nuclear receptor that has been found to modulate the expression of genes involved in synthesis of cytokines and crucial in managing the immune functions of the body [5–7]. Evidence shows that the receptors for vitamin D are found on the immune cells as well as on the epithelium of the bronchus and pulmonary tree [8–11]. Following an infection and binding of toll-like receptors (TLRs), the vitamin D receptors are upregulated and vitamin D by binding to its receptor activates varied endogenous antimicrobial peptides such as cathelicidin LL-37 and β-defensin and suppresses extracellular matrix degrading enzymes like matrix metalloproteinases [4,12–15]. The peptide LL37 interacts with the bacterial wall following which it perforates the cytoplasmic membrane, leading to death of the bacterial cell [16]. In support of the fact, a study by Mily et al. reported that 5000 IU of vitamin D orally and phenylbutyrate 500 mg twice daily increased the synthesis of LL-37 in both macrophages and lymphocytes, further leading to enhanced intracellular killing of MTB by macrophages [17,18].
Intralesional injection of vitamin D in verruca vulgaris increases cathelicidin (LL37) expression; therapeutic and immunohistochemical study
Published in Journal of Dermatological Treatment, 2022
Neveen E. Sorour, Fatma M. Elesawy, Asmaa G. Abdou, Sara E. Abdelazeem, Essam M. Akl
The results of the present study revealed a significant relationship between the degree of LL37 expression after vitamin D injection and the clinical response suggesting its role in the pathogenesis of the disease. Experimental pieces of evidence suggest that LL-37 mediates its antiviral properties by disrupting and damaging the viral envelope in enveloped viruses (21) or by decreasing viral replication in the case of rhinovirus infected cystic fibrosis cell (18). In addition to its antiviral properties, Cathelicidin peptides activate the innate immune system of host cells in response to microbes. They act through multiple specific cell surface receptors such as TLR4 (Toll-like receptor 4), EGFR (epidermal growth factor receptor) and FPRL1(formyl peptide receptor-like -1) (22) to induce keratinocyte migration (23), angiogenesis (24) and stimulates IL-8 secretion from epidermal keratinocytes (25).