scholarly journals Arginase activity in alternatively activated macrophages protects PI3Kp110δ deficient mice from dextran sodium sulfate induced intestinal inflammation

2014 ◽  
Vol 44 (11) ◽  
pp. 3353-3367 ◽  
Author(s):  
Shelley B. Weisser ◽  
Lisa K. Kozicky ◽  
Hayley K. Brugger ◽  
Eyler N. Ngoh ◽  
Bonnie Cheung ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Dextran Sodium Sulfate ◽  
Arginase Activity ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Deficient Mice ◽  
Alternatively Activated

MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis

2005 ◽  
Vol 40 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Akihiro Araki ◽  
Takanori Kanai ◽  
Takahiro Ishikura ◽  
Shin Makita ◽  
Koji Uraushihara ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Dextran Sodium Sulfate ◽  
Deficient Mice

scholarly journals Interdependence between Chromogranin-A, Alternatively Activated Macrophages, Tight Junction Proteins and the Epithelial Functions. A Human and In-Vivo/In-Vitro Descriptive Study

2020 ◽  
Vol 21 (21) ◽  
pp. 7976
Author(s):  
Nour Eissa ◽  
Hayam Hussein ◽  
Diane M. Tshikudi ◽  
Geoffrey N. Hendy ◽  
Charles N. Bernstein ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Chromogranin A ◽  
Intestinal Inflammation ◽  
Collagen Deposition ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Alternatively Activated

Background: Ulcerative colitis (UC) is characterized by altered chromogranin-A (CHGA), alternatively activated macrophages (M2) and intestinal epithelial cells (IECs). We previously demonstrated that CHGA is implicated in colitis progression by regulating the macrophages. Here, we investigated the interplay between CHGA, M2, tight junctions (TJ) and IECs in an inflammatory environment. Methods: Correlations between CHGA mRNA expression of and TJ proteins mRNA expressions of (Occludin [OCLN], zonula occludens-1 [ZO1], Claudin-1 [CLDN1]), epithelial associated cytokines (interleukin [IL]-8, IL-18), and collagen (COL1A2) were determined in human colonic mucosal biopsies isolated from active UC and healthy patients. Acute UC-like colitis (5% dextran sulphate sodium [DSS], five days) was induced in Chga-C57BL/6-deficient (Chga−/−) and wild type (Chga+/+) mice. Col1a2 TJ proteins, Il-18 mRNA expression and collagen deposition were determined in whole colonic sections. Naïve Chga−/− and Chga+/+ peritoneal macrophages were isolated and exposed six hours to IL-4/IL-13 (20 ng/mL) to promote M2 and generate M2-conditioned supernatant. Caco-2 epithelial cells were cultured in the presence of Chga−/− and Chga+/+ non- or M2-conditioned supernatant for 24 h then exposed to 5% DSS for 24 h, and their functional properties were assessed. Results: In humans, CHGA mRNA correlated positively with COL1A2, IL-8 and IL-18, and negatively with TJ proteins mRNA markers. In the experimental model, the deletion of Chga reduced IL-18 mRNA and its release, COL1A2 mRNA and colonic collagen deposition, and maintained colonic TJ proteins. Chga−/− M2-conditioned supernatant protected caco-2 cells from DSS and oxidative stress injuries by improving caco-2 cells functions (proliferation, viability, wound healing) and by decreasing the release of IL-8 and IL-18 and by maintaining the levels of TJ proteins, and when compared with Chga+/+ M2-conditioned supernatant. Conclusions: CHGA contributes to the development of intestinal inflammation through the regulation of M2 and epithelial cells. Targeting CHGA may lead to novel biomarkers and therapeutic strategies in UC.

scholarly journals Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3311-3320 ◽  
Author(s):  
Silke Huber ◽  
Reinhard Hoffmann ◽  
Femke Muskens ◽  
David Voehringer
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Inhibitory Activity ◽  
Th2 Cells ◽  
T Cell Proliferation ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Deficient Mice ◽  
Alternatively Activated

Abstract Alternatively activated macrophages (AAM) accumulate in tissues during Th2-associated immune responses like helminth infections and allergic disorders. These cells differentiate in response to interleukin 4 (IL-4)/IL-13–mediated activation of Stat6 and possess potent inhibitory activity against T cells. The molecular mechanism that leads to T-cell suppression remains unclear and could involve soluble factors or inhibitory ligands. Microarray analysis revealed that the inhibitory ligand, programmed death ligand 2 (PD-L2) was strongly induced by IL-4 in macrophages from wild-type but not Stat6-deficient mice. PD-L2 expression correlated with other established markers for AAM-like Relm-α/Fizz1, arginase1, or Ym1 and thereby serves as useful surface marker to identify and isolate AAM from tissues. Antibodies against PD-L2 blocked the inhibitory activity of AAM and retroviral expression of PD-L2 in macrophages from Stat6−/− mice was sufficient to inhibit T-cell proliferation, which demonstrates that PD-L2 mediates potent and nonredundant inhibition of T cells independently of other Stat6-regulated genes. Infection of conditional IL-4/IL-13–deficient mice with the helminth Nippostrongylus brasiliensis further showed that PD-L2 expression was dependent on IL-4/IL-13 from Th2 cells. In vivo blockade of PD-L2 during N brasiliensis infection caused an enhanced Th2 response in the lung, indicating that AAM inhibit Th2 cells by expression of PD-L2.

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