Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions

Austermann, Judith; Friesenhagen, Judith; Fassl, Selina Kathleen; Petersen, Beatrix; Ortkras, Theresa; Burgmann, Johanna; Barczyk-Kahlert, Katarzyna; Faist, E.; Zedler, Siegfried; Pirr, Sabine; Rohde, Christian; Müller‐Tidow, Carsten; Köckritz-Blickwede, Maren von; Kaisenberg, Constantin S. von; Flohé, Stefanie B.; Ulas, Thomas; Schultze, Joachim L.; Roth, Johannes; Vogl, Thomas; Viemann, Dorothee

doi:10.1016/j.celrep.2015.04.040

Cited by 18 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is underlined by the finding that S100A8/A9 induces Wnt signalling, which has been shown to promote bone formation . These findings are in agreement with other studies that address a more immunomodulatory rather than only a proinflammatory effect of S100A8/A9( and personal unpublished findings).…”

Section: Alarmins In Osteoarthritissupporting

confidence: 93%

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Bosch

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease‐modifying therapy is available. For a long time, OA was considered a non‐inflammatory disease that was the result of ‘wear‐and‐tear’ and abnormal mechanics, and therefore many considered the term ‘osteoarthritis’ a misnomer. However, during the last decades the notion arose that inflammation is not only present in the majority of OA patients but, rather, actively involved in the progression of the disease. Influx of immune cells is observed in the synovium and a plethora of inflammatory mediators is present in tissues and fluids from OA patients. These mediators cause the production of degrading enzymes that break down the cartilage matrix, which is the main hallmark of OA. Alarmins, which belong to the group of danger signals, have been implicated in many inflammatory diseases. They are among the first factors to be released upon cell stress due to, for example, infection, damage and inflammation. They attract and activate cells of the immune system and therefore lie at the base of the inflammatory reaction. In this narrative review, an overview of the history of OA, the evolving concept of inflammation as important factor in the OA pathogenesis, and particularly the central role that alarmins play in the initiation and maintenance of the low‐grade inflammatory response in OA, is provided. Moreover, the targeting of alarmins as a promising approach to dampen the inflammation in OA is highlighted.

show abstract

Section: Alarmins In Osteoarthritissupporting

confidence: 93%

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Bosch

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Moreover, an inhibitor of NF-κB partially reversed the activation of nF-κB and expression of inflammatory cytokines induced by S100A8 in the inflammatory microenvironment. Several studies have reported that S100A8 activated NF-κB in a TLR4-dependent manner (25,44). Although we found that LPS and/or S100A8 treatment could elevate the activation of TLR4, to substantiate this idea, neutralization of TLR4 should be used to block TLR4 signaling and elucidate the mechanisms of S100A8 in CRC progression through the TLR4/nF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 45%

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

Zha

Sun

et al. 2016

Oncology Reports

View full text Add to dashboard Cite

Abstract.Previous studies have shown that S100 calcium-binding protein A8 (S100A8) contributes to the survival and migration of colorectal cancer (CRC) cells. However, whether S100A8 participates in the progression and metastasis of CRC via the regulation of macrophages in the tumor inflammatory microenvironment remains unknown. In this study, phorbol myristate acetate (PMA) was used to induce the differentiation of THP-1 monocytes to macrophages. MTT assay, western blot analysis, immunofluorescence staining, semi-quantitative RT-PCR (semi-PCR), quantitative real-time PCR (qPCR), Gaussia luciferase activity assay and ELISA were performed to analyze the roles and molecular mechanisms of S100A8 in the modulation of macrophages. MTT assay, flow cytometric analysis, Hoechst staining, wound healing and Transwell migration assay were used to test the effect of S100A8 on the viability and migration of CRC cells co-cultured with macrophages in the inflammatory microenvironment. We found that THP-1 monocytes were induced by PMA and differentiated to macrophages. S100A8 activated the NF-κB pathway in the macrophages and promoted the expression of miR-155 and inflammatory cytokines IL-1β and TNF-α in the inflammatory microenvironment mimicked by lipopolysaccharides (LPS). Furthermore, S100A8 contributed to augment the migration but not the viability of the CRC cells co-cultured with the macrophages in the inflammatory microenvironment. Altogether, our study demonstrated that S100A8 facilitated the migration of CRC cells in the inflammatory microenvironment, and the underlying molecular mechanisms may be partially attributed to the overexpression of miR-155, IL-1β and TNF-α through activation of the NF-κB pathway in macrophages. IntroductionColorectal cancer (CRC), for which distant metastasis accounts for the leading cause of cancer mortality, is one of the most malignant gastrointestinal carcinomas worldwide (1). The pathogenesis of CRC is a complex process and involves environmental influences, genetic alterations, and the host immune system and their interactions. The formation of an inflammatory microenvironment also plays a pivotal role in the development of CRC (2). The host microenvironment is comprised of numerous infiltrating immune cell types and resident tumor cells. Among the immune cells, macrophages play an indispensable role. For instance, macrophage infiltration in colon tissue has been observed in both inflammatory bowel disease (IBD) and CRC (4), and the cytokines secreted by macrophages under certain conditions have directly or indirectly stimulated inflammation and tumor progression (5,6). Although great progress has been made, the interactions and the molecular mechanisms between CRC and the inflammatory microenvironment remain unknown. S100A8 (calgranulin A or S100 calcium-binding protein A8) is a member of the low-molecular calcium binding S100 protein family. It also belongs to the family of damage-associated molecular patterns (DAMPs). Studies have shown that S100A8 plays an important role in regul...

show abstract

“…We have previously shown that the alarmins S100A8 and S100A9 are massively released by neonatal monocytes (Mos) upon birth. S100A8/S100A9 serum levels in neonates reach normal adult levels not before the second week of life (6). They are specifically expressed by myeloid cells and have proinflammatory as well as tolerizing effects on different innate immune cells, especially monocytes (Mos) (6-10).…”

mentioning

confidence: 99%

In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock

et al. 2016

Self Cite

View full text Add to dashboard Cite

The high susceptibility of newborn infants to sepsis is ascribed to an immaturity of the neonatal immune system, but the molecular mechanisms remain unclear. Newborn monocytes massively release the alarmins S100A8/S100A9. In adults, these are major regulators of immunosuppressive myeloid-derived suppressor cells (MDSCs). We investigated whether S100A8/S100A9 cause an expansion of monocytic MDSCs (Mo-MDSCs) in neonates, thereby contributing to an immunocompromised state. Mo-MDSCs have been assigned to CD14/human leukocyte antigen (HLA)-DR/CD33 monocytes in humans and to CD11b/Gr-1/Ly6G/Ly6C cells in mice. We found monocytes with these phenotypes significantly expanded in their respective newborns. Functionally, however, they did not prove immunosuppressive but rather responded inflammatorily to microbial stimulation. Their expansion did not correlate with high S100A8/S100A9 levels in cord blood. Murine studies revealed an excessive expansion of CD11b/Gr-1/Ly6G/Ly6C monocytes in S100A9 neonates compared to wild-type neonates. This strong baseline expansion was associated with hyperinflammatory responses during endotoxemia and fatal septic courses. Treating S100A9 neonates directly after birth with S100A8/S100A9 alarmins prevented excessive expansion of this inflammatory monocyte population and death from septic shock. Our data suggest that a specific population of inflammatory monocytes promotes fatal courses of sepsis in neonates if its expansion is not regulated by S100A8/S100A9 alarmins.-Heinemann, A. S., Pirr, S., Fehlhaber, B., Mellinger, L., Burgmann, J., Busse, M., Ginzel, M., Friesenhagen, J., von Köckritz-Blickwede, M., Ulas, T., von Kaisenberg, C. S., Roth, J., Vogl, T., Viemann, D. In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock.

show abstract

Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions

Cited by 18 publications

References 0 publications

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock

Contact Info

Product

Resources

About