Molecular and genetic inflammation networks in major human diseases

Abstract

It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured most critical inflammation involved molecules, genetic susceptibilities, epigenetic factors, and environmental exposures, our schemata on role of inflammation in complex disease, remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the inflammation molecular and genetic networks underlying major human diseases. In this Review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer Disease, Parkinson disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic inflammation networks, which hold a great promise in transiting network snapshots to video-style multi-scale interplays of disease mechanisms, in turn leading to effective clinical intervening.

Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm

“…We view each protein as a surrogate for all proteins in its class. For example, although we found inflammatory signals for TNF‐α, IL‐8, and ICAM‐1, we prefer not to focus on these specific proteins, but rather on broader inflammatory processes (Lai et al, 2015; Zhao et al, 2016). Similarly, we view each angio‐neurotrophic protein as a surrogate for many other proteins that possess neurotrophic and angiogenic characteristics.…”

Inflammatory response and treatment tolerance of long‐term infusion of the anti‐GD2 antibody ch14.18/CHO in combination with interleukin‐2 in patients with high‐risk neuroblastoma

“…The underlying mechanisms of the increased treatment tolerance in subsequent cycles are still not understood. For inflammatory bowel disease, diabetes, and cancer, an aberrant type 1 and/or type 2 immunity was identified to play a key role in the pathophysiology and for disease progression, and the existence of a network of regulatory cytokines and immune cells has important implications in this context. IL‐2 is a type 1 cytokine.…”

Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation

“…However, inflammation may have a negative impact on health if it is extreme or continuously repeats [8]. Chronic inflammation can cause a variety of conditions, such as rheumatoid arthritis, cardiovascular disease and cancer [9].…”