Stromal cell regulation of inflammatory responses

2022 ◽  
Vol 74 ◽  
pp. 92-99
Jasna Friščić ◽  
Markus H Hoffmann
Placenta ◽  
2015 ◽  
Vol 36 (9) ◽  
pp. A55
Laura James-Allan ◽  
Alison Wallace ◽  
Guy Whitley ◽  
Judith Cartwright

2014 ◽  
Vol 111 (11) ◽  
pp. 2239-2251 ◽  
Jeffrey A. Barminko ◽  
Nir I. Nativ ◽  
Rene Schloss ◽  
Martin L. Yarmush

Diabetes ◽  
2020 ◽  
pp. db191050
Terri C. Thayer ◽  
Joanne Davies ◽  
James A. Pearson ◽  
Stephanie J. Hanna ◽  
Li Wen ◽  

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S31-S31
Ingrid Jurickova ◽  
Elizabeth Novak ◽  
Elizabeth Angerman ◽  
Erin Bonkowski ◽  
Kevin Mollen ◽  

Abstract Introduction The DUOX2 intestinal epithelial NADPH oxidase is upregulated in Crohn’s Disease (CD), and DUOX2 mutations are associated with increased CD risk. Oxidative stress and loss of mitochondrial function disrupt the intestinal barrier promoting inflammatory responses to commensals. The relative impact of DUOX2 mutations and microbial products in this regard is poorly understood. Hypothesis We hypothesized that DUOX2 genetic variation would be associated with differences in cellular reactive oxygen species (ROS) production and mitochondrial function in a Human Intestinal Organoid (HIO) model system. Methods Induced pluripotent stem cell lines derived from pediatric CD patients with and without combined DUOX2 missense mutations(R701Q, P982A, and H678R) were used to generate wild type (WT) and DUOX2mut HIOs. Reactive oxygen species (ROS) production was measured using the two-color ROS-ID® Total ROS/Superoxide detection kit, and the mitochondrial membrane potential (MMP) was measured using JC1 staining by flow cytometry in HIO EpCAM+ epithelial cells and CD90+ stromal cells. Expression of inflammatory and mitochondrial genes which varied with DUOX2 mutation carriage in CD patent ileal biopsies was measured by RT-PCR. HIO mitochondrial complex I and II activity was measured using an Oroboros respirometer. Results Epithelial ROS production was reduced in DUOX2mut HIO under basal conditions; this difference was not observed following pyocyanin stimulation (Fig. 1A). A profound suppression of epithelial ROS production was observed following butyrate treatment. Butyrate did not alter stromal cell ROS production. Under these conditions, induction of ROS by pyocyanin was abrogated in WT, but not DUOX2mut HIO epithelial cells (Fig. 1B). Butyrate increased expression of core genes regulating the mitochondrial respiratory chain and DNA synthesis (COX5B, NDUFA1, POLG2, SLC25A27) and HIF1A implicated in barrier function, independent of genotype (p<0.05). The epithelial and stromal cell mitochondrial membrane potential (MMP) (Fig. 2A), and HIO mitochondrial complex I activity (Fig. 2B), were reduced in DUOX2mut HIO under basal conditions. This was specific, as mitochondrial complex II activity did not vary with DUOX2 genotype. Conclusions We confirmed epithelial effects of DUOX2 genotype and butyrate exposure on ROS production in the HIO model system. Genotype dependent effects on basal ROS production were largely abrogated by the microbial products pyocyanin and butyrate, although butyrate inhibition of pyocyanin induced ROS production was dependent on intact DUOX2 function. Data suggest a previously unanticipated effect of DUOX2 genetic variation on the epithelial and stromal cell MMP and cellular respiration. This may have implications for mechanisms by which DUOX2 regulates barrier function and inflammatory responses to commensals in CD.

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 937-945 ◽  
Adrian R. L. Gear ◽  
Sudawadee Suttitanamongkol ◽  
Delia Viisoreanu ◽  
Renata K. Polanowska-Grabowska ◽  
Sanghamitra Raha ◽  

Abstract Platelet activation is normally induced by primary agonists such as adenosine diphosphate (ADP), thrombin, and collagen, whereas other agonists, such as epinephrine, can play important accessory roles. It is now reported that the macrophage-derived chemokine (MDC), thymus activation–regulated chemokine (TARC), and stromal cell–derived factor one (SDF-1) are highly effective activators of platelet function under a variety of conditions, stimulating platelet shape change, aggregation, and adhesion to collagen or fibrinogen. Chemokine-mediated platelet activation was rapid and maximal (less than 5 seconds) under arterial flow conditions and depended strongly on the presence of low levels of primary agonists such as ADP or thrombin. Concentrations of ADP (0.05-0.25 μM) or thrombin (0.005-0.02 U/mL) that induced minimal aggregation caused major aggregation acting in combination with the chemokines. The ability of apyrase to block chemokine-dependent aggregation or adhesion was consistent with an important role for ADP. Chemokine-stimulated aggregation was also insensitive to indomethacin, suggesting that the activation of cyclo-oxygenase is not involved. TARC, MDC, and SDF-1 increased intracellular calcium concentrations [Ca2+]iwhen combined with low levels of ADP. The MDC and TARC receptor CCR4 was expressed on platelets, and an anti-CCR4 antibody blocked aggregation induced by TARC or MDC. Treatment of platelets with SDF-1 and MDC rapidly exposed P-selectin (CD62P) on the cell surface but did not induce the secretion of serotonin. These findings suggest that the chemokines MDC, TARC, and SDF-1, which may be produced during inflammatory responses, coupled with low levels of ADP or thrombin, can serve as strong stimuli for activating platelet function.

Immunology ◽  
2013 ◽  
Vol 140 (1) ◽  
pp. 12-21 ◽  
Matthew J. W. Kain ◽  
Benjamin M. J. Owens

2007 ◽  
Vol 85 (10) ◽  
pp. 1047-1056 ◽  
Claude Roth ◽  
Carla Rothlin ◽  
Sylvain Riou ◽  
David H. Raulet ◽  
Greg Lemke

2019 ◽  
Vol 156 (6) ◽  
pp. S-41
Gabriela Uribe ◽  
Kamil Khanipov ◽  
Georgiy Golovko ◽  
Romain Villéger ◽  
Carl Grim ◽  

1995 ◽  
Vol 268 (5) ◽  
pp. L856-L861 ◽  
N. W. Lukacs ◽  
S. L. Kunkel ◽  
R. Allen ◽  
H. L. Evanoff ◽  
C. L. Shaklee ◽  

Chronic inflammatory responses in the lung rely on the continual recruitment of leukocytes to the site of inflammation. Recent data have demonstrated a possible role for stromal cell-derived chemokines in leukocyte recruitment. In the present study we examined the production of interleukin (IL)-8 and ENA-78, members of the C-X-C family of chemokines, and macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, members of the C-C chemokine family, from pulmonary smooth muscle and endothelial cells. The production of IL-8 and ENA-78 was induced by early response cytokines, IL-1 and tumor necrosis factor (TNF), but not by immune-associated cytokines, IL-4, IL-10, or interferon (IFN)-gamma. In contrast, the production of MIP-1 alpha and MIP-1 beta by pulmonary vascular smooth muscle cells increased when stimulated by immune-associated cytokines as well as with IL-1 beta and TNF. The level of MIP-1 alpha production induced in smooth muscle cells by the immune-associated cytokines, IL-4, IFN-gamma, and IL-10 ranged from 0 to 340 pg/ml. The production of MIP-1 beta in response to the immune-associated cytokines IL-4, IFN-gamma, and IL-10 in smooth muscle cells ranged from 260 to 940 pg/ml. Human pulmonary artery endothelial cells did not generate MIP-1 alpha or MIP-1 beta in response to graded doses of any of the cytokines. These data demonstrate differential induction of C-X-C and C-C chemokines from nonimmune stromal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

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