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Front. Physiol. | doi: 10.3389/fphys.2018.01825

Editorial: Integrative Approaches to the Molecular Physiology of Inflammation

  • 1Computational Genomics, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico
  • 2Instituto Nacional de Cardiologia Ignacio Chavez, Mexico
  • 3Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico

Inflammation is the generic name given to a number of complex biological processes related to the organismal response to a disparate set of stimuli (most of them harmful or pathogenic), either intrinsic (DNA damage, metabolic deregulation, etc.) or extrinsic (pathogens, irritants, etc.) in nature. Such processes are commonly related to a protective reaction to disease related events that involve immune response, vascularization, and cellular signaling among many other features. Recent years have witnessed an increased interest in the study of inflammation, since it was discovered that inflammatory processes are associated with a growing number of pathologies, many of which had not been previously classified as “inflammatory”.

Complex chronic diseases such as cancer, diabetes, or even Alzheimer's or Parkinson's have recently been discovered to be strongly associated with inflammatory responses. Other maladies such as cardiovascular, rheumatic and autoimmune diseases have been traditionally studied from the standpoint of inflammation. Processes such as the ones leading to aging and fragility or even hormone dysfunctions are also starting to be related to inflammatory responses.

For the reasons mentioned above, an important goal in contemporary biomedical science is the integrated study of the physiology of inflammation and the molecular pathways associated with it. The aim of this Research Topic is hence to gather contributions from the many different fields and approaches to the physiology and the molecular origins of inflammation; particularly those that may be involved in the development and evolution of diseased phenotypes. By presenting them together we want to cooperate to unveil the commonalities and differences that so many of these phenomena have, particularly in relation to their molecular origins as well as to any issues that may enlighten prognostics, diagnostics and therapeutic decisions.

We believe that this Research Topic on Integrative Approaches to the Molecular Physiology of Inflammation is a good selection of the wide scope and multiple (seemingly disparate but often convergent) views to approach the molecular origins of complex inflammatory phenotypes. It consists on 24 articles: 17 original research contributions and 7 review articles (5 reviews, 1 systematic review and 1 minireview). Both, the research papers and the reviews provide varied and insightful approaches to the different facets of inflammation with approaches ranging from general inflammation and signaling depictions deeply rooted on functional biology and physiology, to computational systems biology analyses, translational medicine and pharmacological explorations. Model systems are also quite diverse: human subjects, mice and other mammal models, cell cultures and in silico, complex networks and database studies.

These systems allowed the analysis of questions that include: dissecting the inflammatory components of complex disease phenotypes, such is the case of the review by Homme, et al. on diabetic retinopathy and its relationship with pyroptosis as well as downstream products of inflammation; and of the research paper by Sheffield and coworkers, where they present their findings on how deregulation of inflammation leads to changes in cartilage homeostasis with strong consequences for Bardet-Biedl cilliopathy.

A functional approach to study differential signaling networks related to autocrine processes in hepatic stellate cells and hepatocytes under stress is presented by Vodovotz, et al. The authors were able to differentiate between networks associated with intracellular information processing (“thinking”) and networks devoted to extracellular information transfer (“talking”), whose interplay results determinant for the differences in autocrine response in both cell types. Also in connection with systemic signaling regulation, the research paper by Bösl and collaborators provide a nice example of cooperative signaling by two TLRs, enhancing the regulatory processes in a way no single receptor cascades may actually achieve.

The relation between metabolic processes in the muscular tissue and inflammation is further discussed in the research paper by Kim and coworkers on IL-1β production in vascular smooth muscle cells and in the work by Miao, et al. on the attenuation of cancer cachexia by crosstalk induction by inflammation products.

The molecular origins of inflammatory processes affecting the architecture and function of the endothelium have also been covered in this special issue: On the one hand, the work of Wang and Lo identifies the action of the basic fibroblast growth factor on protecting the laminar shear flow medium of the arteries from the action of TNF-alpha induced endothelial dysfunction.

Neurological disorders have also been linked to non-resolved inflammation scenarios. In this regard, an integrative computational approach by the group of Del Sol shows how the analysis of molecular networks involved in inflammation led to the discovery of specific sites linked to Alzheimer’s disease. Mathematical and computational models are increasingly providing insight, not only in the pathophysiology of inflammation and its influence on disease but are also helpful in the development of systematic therapeutics. Particularly useful are approaches that allow drug repurposing, since these provide a significantly faster and easier transition from research findings to patients’ treatment. The work by de Anda-Jáuregui and collaborators provides a powerful example of high-throughput computational analysis of massive experimental databases combined with a network approach to the repositioning of anti-inflammatory drugs.

The development of novel therapeutic strategies and pharmacological approaches for the modulation of inflammatory processes is deeply covered in this research topic. Gao, Yang and their collaborators contributed with a review that covers some of the therapeutic uses of the TLR signaling pathway in the development of anti-inflammatory therapeutics based on molecular approaches going up to nanomedicine. There are also a number of research papers dealing with pharmacological and therapeutical developments to treat inflammation. In their contribution, Zhang and collaborators showed that by an epigenomic mechanism of miR-29b-3p-mediated inhibition of HMGB1/TLR4 carnosic acid is able to alleviate liver fibrosis in an animal model. The use of isoproterenol to modify aortic vasoreactivity and VCAM-1 modulation was investigated in an animal model and reported by Nieto-Lima and co-workers. They found important age and gender associations between drug dose and response to the treatment.

Together, these articles provide a sample of the multiple and complex roles of inflammation and its involvement in infections, immunity, and multiple pathological conditions. They also provide guidance for novel therapeutic approaches and future research on the physiology of inflammation.

Keywords: Inflammation, Molecular Physiology, Integrative biology, Immunity, Pathophyisology

Received: 25 Oct 2018; Accepted: 06 Dec 2018.

Edited by:

Geoffrey A. Head, Baker Heart and Diabetes Institute, Australia

Reviewed by:

Kulmira Nurgali, Victoria University, Australia, Australia  

Copyright: © 2018 Hernandez-Lemus, Soto and ROSALES. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Enrique Hernandez-Lemus, Instituto Nacional de Medicina Genómica (INMEGEN), Computational Genomics, Mexico City, Mexico,