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Role of Interleukin Genes in Etiopathogenesis of Multifactorial Traits and Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 17695

Special Issue Editor

Prof. Lydie Izakovicova Holla

E-Mail Website
Guest Editor
Department of Pathophysiology and Stomatology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
Interests: multifactorial diseases; molecular biology; molecular genetics; medical statistics

Special Issue Information

Dear Colleagues,

In the last decade, interleukins have been an interesting topic in many fields of medicine. They play pivotal roles during infection, trauma, cancer, and inflammation; and they participate in the control of cellular proliferation, differentiation, survival, or death. Interleukins expression is regulated at chromatin remodeling, transcription, and post-transcription levels. Variability in the interleukin genes and/or their receptors has been associated with several multifactorial traits and/or diseases; a number of these cytokines have been considered as targets for the development of biological therapies, with the goal of blocking their activities and modulating the immune response.

We invite authors to contribute to this Special Issue of the International Journal of Molecular Sciences entitled “Role of Interleukin Genes in the Etiopathogenesis of Multifactorial Traits and Diseases” with original research and review articles focusing on, but not limited to, molecular levels—that is, genetic (the role of rare and common genetic variants in traits or disease–gene associations) and epigenetic mechanisms, functional studies, in vitro and in vivo models, and mechanisms of proinflammatory/anti-inflammatory responses. In addition, because unravelling the interplay between environmental factors (e.g., infections) and the genetic variation in a population is crucial for understanding the pathogenesis of common autoimmune or infectious diseases and for designing novel therapeutic strategies, insights into the investigation of host–pathogen interactions are also invited.

We believe that a series of articles within this framework will make a valuable contribution to a better understanding of this very important, rapidly developing, and still not fully understand field of multifactorial traits and/or disease research. 

Prof. Lydie Izakovicova Holla, M.D., Ph.D.
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • interleukin gene
  • mutation
  • polymorphism
  • multifactorial (common) disease
  • epigenetic mechanisms
  • immune reaction
  • inflammation
  • host–pathogen interaction

Published Papers (5 papers)

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Research

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14 pages, 3224 KiB  
Article
Autoantibodies from Patients with Scleroderma Renal Crisis Promote PAR-1 Receptor Activation and IL-6 Production in Endothelial Cells
by Michèle Simon, Christian Lücht, Isa Hosp, Hongfan Zhao, Dashan Wu, Harald Heidecke, Janusz Witowski, Klemens Budde, Gabriela Riemekasten and Rusan Catar
Int. J. Mol. Sci. 2021, 22(21), 11793; https://doi.org/10.3390/ijms222111793 - 30 Oct 2021
Cited by 15 | Viewed by 2092
Abstract
Background. Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased [...] Read more.
Background. Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its role in SRC is unclear. Here, we aimed to determine how the autoantibodies from patients with SSc and SRC affect IL-6 secretion by micro-vascular endothelial cells (HMECs). Methods. Serum IgG fractions were isolated from either SSc patients with SRC (n = 4) or healthy individuals (n = 4) and then each experiment with HMECs was performed with SSc-IgG from a separate patient or separate healthy control. IL-6 expression and release by HMECs was assessed by quantitative reverse transcription and quantitative PCR (RT-qPCR) and immunoassays, respectively. The mechanisms underlying the production of IL-6 were analyzed by transient HMEC transfections with IL-6 promoter constructs, electrophoretic mobility shift assays, Western blots and flow cytometry. Results. Exposure of HMECs to IgG from SSc patients, but not from healthy controls, resulted in a time- and dose-dependent increase in IL-6 secretion, which was associated with increased AKT, p70S6K, and ERK1/2 signalling, as well as increased c-FOS/AP-1 transcriptional activity. All these effects could be reduced by the blockade of the endothelial PAR-1 receptor and/or c-FOS/AP-1silencing. Conclusions. Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signalling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC. Full article
(This article belongs to the Special Issue Role of Interleukin Genes in Etiopathogenesis of Multifactorial Traits and Diseases)
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Review

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13 pages, 1314 KiB  
Review
Involvement of Molecular Mechanisms between T/B Cells and IL-23: From Palmoplantar Pustulosis to Autoimmune Diseases
by Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Atsushi Enomoto, Kiyoshi Miyagawa, Shinichi Sato and Ayumi Yoshizaki
Int. J. Mol. Sci. 2022, 23(15), 8261; https://doi.org/10.3390/ijms23158261 - 27 Jul 2022
Cited by 12 | Viewed by 2521
Abstract
Palmoplantar pustulosis (PPP) is a disease that causes recurrent blisters and aseptic pustules on the palms and soles. It has been suggested that both innate and acquired immunity are involved. In particular, based on the tonsils and basic experiments, it has been assumed [...] Read more.
Palmoplantar pustulosis (PPP) is a disease that causes recurrent blisters and aseptic pustules on the palms and soles. It has been suggested that both innate and acquired immunity are involved. In particular, based on the tonsils and basic experiments, it has been assumed that T and B cells are involved in its pathogenesis. In addition, the results of clinical trials have suggested that IL-23 is closely related to the pathogenesis. This review describes PPP and the genetic background, the factors involved in the onset and exacerbation of disease and its relation to the molecular mechanism. In addition, we describe the usefulness of biological therapy and its implications in relation to the importance in pathology, the pathogenesis of PPP, the importance of the role of the IL-23–Th17 axis and IL-36 in PPP. Furthermore, we describe an animal experimental model of PPP, the efficacy and mechanism of action of guselkumab, an anti-IL-23 antibody, the latest research, and finally the possibility for it to be effective for other autoimmune diseases. Full article
(This article belongs to the Special Issue Role of Interleukin Genes in Etiopathogenesis of Multifactorial Traits and Diseases)
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26 pages, 1701 KiB  
Review
The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature
by Konstantinos Pantos, Sokratis Grigoriadis, Evangelos Maziotis, Kalliopi Pistola, Paraskevi Xystra, Agni Pantou, Georgia Kokkali, Athanasios Pappas, Maria Lambropoulou, Konstantinos Sfakianoudis and Mara Simopoulou
Int. J. Mol. Sci. 2022, 23(4), 2198; https://doi.org/10.3390/ijms23042198 - 16 Feb 2022
Cited by 32 | Viewed by 5355
Abstract
Recurrent implantation failure (RIF) is a multifactorial condition affecting 10–15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to [...] Read more.
Recurrent implantation failure (RIF) is a multifactorial condition affecting 10–15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients. Full article
(This article belongs to the Special Issue Role of Interleukin Genes in Etiopathogenesis of Multifactorial Traits and Diseases)
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26 pages, 2609 KiB  
Review
IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives
by Michal Španko, Karolína Strnadová, Aleš Jan Pavlíček, Pavol Szabo, Ondřej Kodet, Jaroslav Valach, Barbora Dvořánková, Karel Smetana, Jr. and Lukáš Lacina
Int. J. Mol. Sci. 2021, 22(20), 11027; https://doi.org/10.3390/ijms222011027 - 13 Oct 2021
Cited by 15 | Viewed by 3681
Abstract
Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways [...] Read more.
Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer. Full article
(This article belongs to the Special Issue Role of Interleukin Genes in Etiopathogenesis of Multifactorial Traits and Diseases)
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13 pages, 680 KiB  
Review
Interleukin-1β in Multifactorial Hypertension: Inflammation, Vascular Smooth Muscle Cell and Extracellular Matrix Remodeling, and Non-Coding RNA Regulation
by Elaina Melton and Hongyu Qiu
Int. J. Mol. Sci. 2021, 22(16), 8639; https://doi.org/10.3390/ijms22168639 - 11 Aug 2021
Cited by 21 | Viewed by 3017
Abstract
The biological activities of interleukins, a group of circulating cytokines, are linked to the immuno-pathways involved in many diseases. Mounting evidence suggests that interleukin-1β (IL-1β) plays a significant role in the pathogenesis of various types of hypertension. In this review, we summarized recent [...] Read more.
The biological activities of interleukins, a group of circulating cytokines, are linked to the immuno-pathways involved in many diseases. Mounting evidence suggests that interleukin-1β (IL-1β) plays a significant role in the pathogenesis of various types of hypertension. In this review, we summarized recent findings linking IL-1β to systemic arterial hypertension, pulmonary hypertension, and gestational hypertension. We also outlined the new progress in elucidating the potential mechanisms of IL-1β in hypertension, focusing on it’s regulation in inflammation, vascular smooth muscle cell function, and extracellular remodeling. In addition, we reviewed recent studies that highlight novel findings examining the function of non-coding RNAs in regulating the activity of IL-1β and its associated proteins in the setting of hypertension. The information collected in this review provides new insights into understanding the pathogenesis of hypertension and could lead to the discovery of new anti-hypertensive therapies to combat this highly prevalent disease. Full article
(This article belongs to the Special Issue Role of Interleukin Genes in Etiopathogenesis of Multifactorial Traits and Diseases)
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