S100A6 Promotes Inflammation and Infiltration of Mononuclear/Macrophages via the p-P38 and p-JNK Pathways in Acute Liver Injury

He, Tong Chuan; Wang, Li; Zhang, Kefan; Shi, Jing; Wu, Yongshuai; Bao, Yong-Rui; wang, changshan

doi:10.21203/rs.3.rs-1161048/v1

Cited by 3 publications

(2 citation statements)

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“…S100A6 is often detected at sites of inflammation [ 131 ], but there are contradictory reports as to its role in this process [ 132 , 133 ]. On the other hand, numerous data indicate that S100A6 may be involved in tissue/cell repair and regeneration after stress.…”

Section: Structural Aspects Of S100a6—ligand Interactionsmentioning

confidence: 99%

S100A6 Protein—Expression and Function in Norm and Pathology

Leśniak

Filipek

2023

IJMS

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S100A6, also known as calcyclin, is a calcium-binding protein belonging to the S100 protein family. It was first identified and purified more than 30 years ago. Initial structural studies, focused mostly on the mode and affinity of Ca2+ binding and resolution of the resultant conformational changes, were soon complemented by research on its expression, localization and identification of binding partners. With time, the use of biophysical methods helped to resolve the structure and versatility of S100A6 complexes with some of its ligands. Meanwhile, it became clear that S100A6 expression was altered in various pathological states and correlated with the stage/progression of many diseases, including cancers, indicative of its important, and possibly causative, role in some of these diseases. This, in turn, prompted researchers to look for the mechanism of S100A6 action and to identify the intermediary signaling pathways and effectors. After all these years, our knowledge on various aspects of S100A6 biology is robust but still incomplete. The list of S100A6 ligands is growing all the time, as is our understanding of the physiological importance of these interactions. The present review summarizes available data concerning S100A6 expression/localization, interaction with intracellular and extracellular targets, involvement in Ca2+-dependent cellular processes and association with various pathologies.

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Section: Structural Aspects Of S100a6—ligand Interactionsmentioning

confidence: 99%

S100A6 Protein—Expression and Function in Norm and Pathology

Leśniak

Filipek

2023

IJMS

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“…However, this mediator did not appear to be altered in our study. S100-A6 regulates immune homeostasis and is suggested to function as DAMP to activate p38 and JNK downstream of the TLR4 and p65 pathways [100], therefore may promote inflammation and prostaglandin production. This protein was found to be decreased, suggesting a downregulation of the pro-inflamamtory response.…”

Section: Proteins Of Eicosanoid Metabolism and Regulationmentioning

confidence: 99%

SILAC-based quantitative proteomics to investigate the eicosanoid associated inflammatory response in activated macrophages

et al. 2022

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Background Macrophages play a central role in inflammation by phagocytosing invading pathogens, apoptotic cells and debris, as well as mediating repair of tissues damaged by trauma. In order to do this, these dynamic cells generate a variety of inflammatory mediators including eicosanoids such as prostaglandins, leukotrienes and hydroxyeicosatraenoic acids (HETEs) that are formed through the cyclooxygenase, lipoxygenase and cytochrome P450 pathways. The ability to examine the effects of eicosanoid production at the protein level is therefore critical to understanding the mechanisms associated with macrophage activation. Results This study presents a stable isotope labelling with amino acids in cell culture (SILAC) -based proteomics strategy to quantify the changes in macrophage protein abundance following inflammatory stimulation with Kdo2-lipid A and ATP, with a focus on eicosanoid metabolism and regulation. Detailed gene ontology analysis, at the protein level, revealed several key pathways with a decrease in expression in response to macrophage activation, which included a promotion of macrophage polarisation and dynamic changes to energy requirements, transcription and translation. These findings suggest that, whilst there is evidence for the induction of a pro-inflammatory response in the form of prostaglandin secretion, there is also metabolic reprogramming along with a change in cell polarisation towards a reduced pro-inflammatory phenotype. Conclusions Advanced quantitative proteomics in conjunction with functional pathway network analysis is a useful tool to investigate the molecular pathways involved in inflammation.

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