Production of inflammatory cytokines in the intestinal lamina propria

1991 ◽  
Vol 10 (3-4) ◽  
pp. 239-246 ◽  
Author(s):  
Claudio Fiocchi
Keyword(s):  
Lamina Propria ◽  
Inflammatory Cytokines ◽  
Intestinal Lamina Propria

scholarly journals OP39 Treatment of ulcerative colitis With AMT-101, a novel oral interleukin-10 immunomodulatory fusion biologic that traffics across the intestinal epithelium

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S039-S040
Author(s):  
R Mrsny ◽  
B Kanwar ◽  
T Mahmood
Keyword(s):  
Ulcerative Colitis ◽  
Side Effects ◽  
Lamina Propria ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Oral Gavage ◽  
Intestinal Lamina Propria ◽  
Cynomolgus Monkeys ◽  
Pro Inflammatory Cytokines

Abstract Background While different chronic inflammatory diseases can be correlated with distinct pro-inflammatory cytokines, interleukin-10 (IL-10) represents a central anti-inflammatory cytokine capable of modulating many pro-inflammatory signals. Previous clinical efforts to capture the benefit of IL-10 in suppressing the pro-inflammatory state in inflammatory bowel disease (IBD) patients have been limited by dose-limiting systemic side effects. Methods We have designed a chimaera of human IL-10 genetically fused to a non-toxic and poorly immunogenic fragment of the cholix exotoxin, termed AMT-101, that demonstrated rapid receptor-mediated transcytosis in vitro and in vivo and could activate phospho-STAT3 in cells within the lamina propria following luminal administration (data not shown). Mice with oxazolone-induced colitis were dosed by oral gavage with AMT-101 daily for 12 days, at which time colon tissue and serum were examined for hallmarks of inflammation. Enteric-coated capsules were used to deliver either 1 or 5 mg of AMT-101 to the distal ileum of cynomolgus monkeys; serum was collected to examine PK and PD outcomes in this non-inflamed model. Results Histological changes of colonic tissue associated with oxazolone-induced colitis was blocked by the oral gavage of AMT-101. Increases in serum levels of pro-inflammatory cytokines IL-1b, IL-6, and IL-17A were blunted by AMT-101 treatment. Remarkably, endogenous IL-10 increased in this model in an attempt to correct inflammation, but this was also decreased by the delivery of AMT-101. Cynomolgus monkeys dosed orally with AMT-101 capsules showed very low serum levels compared with those observed after IV injection of 0.5 mg/kg AMT-101. Strikingly, serum levels of IL-1 receptor antagonist (IL-1RA) as an anti-inflammatory PD marker were increased to a greater extent following oral capsule dosing compared with IV administration. Conclusion These studies provide strong pre-clinical evidence that AMT-101 can effectively reach the intestinal lamina propria to delivery biologically-active IL-10 following transcytosis across the intestinal epithelium. Importantly, the gut-selective nature of the responses observed suggests AMT-101 may alleviate the previous issues of dose-limiting side effects observed with systemic administration of IL-10 and point to the intestinal lamina propria as a critical site of IL-10’s immunomodulatory actions. AMT-101 has advanced to the clinic and is currently being evaluated in a Phase1b trial in patients with active ulcerative colitis.

scholarly journals Focused Examination of the Intestinal lamina Propria Yields Greater Molecular Insight into Mechanisms Underlying SIV Induced Immune Dysfunction

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34561 ◽  
Author(s):  
Mahesh Mohan ◽  
Deepak Kaushal ◽  
Pyone P. Aye ◽  
Xavier Alvarez ◽  
Ronald S. Veazey ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Immune Dysfunction ◽  
Intestinal Lamina Propria ◽  
Insight Into

scholarly journals Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis

Oncotarget ◽  
2017 ◽  
Vol 8 (58) ◽  
pp. 98945-98952 ◽  
Author(s):  
Fan Wang ◽  
Pai-Lan Peng ◽  
Xue Lin ◽  
Ying Chang ◽  
Jing Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Nk Cells ◽  
Lamina Propria ◽  
Regulatory Role ◽  
Intestinal Lamina Propria ◽  
Th1 Cytokines

scholarly journals Intestinal myofibroblasts: targets for stem cell therapy

2011 ◽  
Vol 300 (5) ◽  
pp. G684-G696 ◽  
Author(s):  
R. C. Mifflin ◽  
I. V. Pinchuk ◽  
J. I. Saada ◽  
D. W. Powell
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Cell Therapy ◽  
Lamina Propria ◽  
Stem Cell Therapy ◽  
Intestinal Inflammation ◽  
Mesenchymal Cells ◽  
Hematopoietic Stem ◽  
Intestinal Lamina Propria

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).

scholarly journals Subclinical Scurvy in the Guinea Pig

1980 ◽  
Vol 17 (1) ◽  
pp. 40-44 ◽  
Author(s):  
G. L. Clarke ◽  
A. M. Allen ◽  
J. D. Small ◽  
A. Lock
Keyword(s):  
Weight Loss ◽  
Guinea Pig ◽  
Lamina Propria ◽  
Guinea Pigs ◽  
Management Practices ◽  
Intestinal Lamina Propria ◽  
Feed Management ◽  
Acute Enteritis

Twenty-eight guinea pigs from nine episodes of subclinical scurvy had diarrhea, weight loss and dehydration. The classical signs of scurvy were not seen. Microscopically the epiphyses were attenuated and irregular. The amount of osteoid was less than normal. Many guinea pigs had acute enteritis. In some there were many hemosiderin-laden macrophages in the intestinal lamina propria. All episodes were associated with either autoclaving food without adequate supplementation or other inadequate feed management practices.

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