Burn injury induces intestinal inflammatory response mediated by Th17 in burn-primed endotoxemic mice

Objective: This study aimed to elucidate the mechanism underlying the susceptibility to infection-related acute lung injury by focusing on the role of gut mucosal T-helper (Th) 17 cells that preferentially produce IL-17 with probiotics in a burn-primed endotoxemic mice model. Methods: Mice were subjected to a 15% total body surface area third-degree burn. Survival from lethal lipopolysaccharide (LPS) administration (3 mg/kg) on 11th day post burn was assessed in mice fed by chow with or without 1.2% Lactobacillus powder after burn injury. Lamina propria mononuclear cells were enzymatically isolated from the ileum removed on 11th day post burn and incubated along with 1 μg/mL LPS or 10 μg/mL anti-CD3 antibody for 24 h; subsequently, the following seven cytokines were analyzed in the supernatant: IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17. Results: Lactobacillus treatment post-burn injury markedly improved survival after lethal endotoxemia in burn-primed mice (64.3% vs. 21.4%, p = 0.03). The production of proinflammatory cytokines such as TNF-α, IL-6, and IL-17 by lamina propria mononuclear T-lymphocytes and macrophages including Th17 response was augmented by burn injury but decreased with Lactobacillus treatment after burn injury. Conclusions: Th17- and Th17-mediated inflammatory responses in the gut mucosa may play a vital role, which could be attenuated by Lactobacillus treatment, in survival of lethal endotoxemia in burn-primed mice.

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Hypertonic saline dextran after burn injury decreases inflammatory cytokine responses to subsequent pneumonia-related sepsis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00586.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. H1642-H1650 ◽

Cited By ~ 12

Author(s):

Jureta W. Horton ◽

David L. Maass ◽

D. Jean White

Keyword(s):

Hypertonic Saline ◽

Burn Injury ◽

Inflammatory Responses ◽

Contractile Function ◽

Total Body Surface Area ◽

Isotonic Saline ◽

Ringer Solution ◽

Myocardial Inflammation ◽

Adult Rats ◽

Tnf Α

The present study examined the hypothesis that hypertonic saline dextran (HSD), given after an initial insult, attenuates exaggerated inflammation that occurs with a second insult. Adult rats ( n = 15 per group) were divided into groups 1 (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) + 4 ml·kg−1·% burn−1 lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR), and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns; groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus pneumoniae (4 × 106 colony-forming units) 7 days after burn. Groups 4–8 were studied 8 days after burn and 24 h after IT septic challenge. When compared with sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD-treated burns. Cardiac inflammatory responses (pg/ml TNF-α) were evident with IS (170 ± 10) but not HSD (45 ± 5) treatment vs. sham treatment (80 ± 15). Pneumonia-related sepsis 8 days after IS-treated burns ( group 7) exacerbated TNF-α responses/contractile dysfunction vs. IS-treated burns in the absence of sepsis ( P < 0.05). Sepsis that occurred after HSD-treated burns ( group 8) had less myocyte TNF-α secretion/better contractile function than IS-treated burns given septic challenge ( group 7, P < 0.05). We conclude that an initial burn injury exacerbates myocardial inflammation/dysfunction occurring with a second insult; giving HSD after the initial insult attenuates myocardial inflammation/dysfunction associated with a second hit, suggesting that HSD reduces postinjury risk for infectious complications.

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In vitro immunomodulation of RH IL-10 on TNF-α secretion by lamina propria mononuclear cells in Crohn's disease

Gastroenterology ◽

10.1016/s0016-5085(98)84390-4 ◽

1998 ◽

Vol 114 ◽

pp. A1079

Author(s):

A. Schmit ◽

M. Carol ◽

A. Van Gossum ◽

M. Goldman ◽

F. Mascart-Lemone

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Lamina Propria ◽

Mononuclear Cells ◽

Lamina Propria Mononuclear Cells ◽

Tnf Α

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Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease

Gut ◽

10.1136/gut.43.2.203 ◽

1998 ◽

Vol 43 (2) ◽

pp. 203-209 ◽

Cited By ~ 75

Author(s):

M Noguchi ◽

N Hiwatashi ◽

Z Liu ◽

T Toyota

Keyword(s):

Lamina Propria ◽

Mononuclear Cells ◽

Tnf Receptor ◽

Tnf Receptors ◽

Lamina Propria Mononuclear Cells ◽

Tnf Α ◽

Soluble Tnf Receptors ◽

Inflammatory Bowel ◽

Soluble Tnf Receptor ◽

Necrosis Factor

Background—Tumour necrosis factor (TNF) α and TNF-β are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD).Aims—To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD.Methods—The secretion of TNF-α, TNF-β, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD.Results—Spontaneous secretion of TNF-α in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-β was higher in patients with Crohn’s disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-α production correlated with severity of disease.Conclusions—Results showed enhanced secretion of TNF-α but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.

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Activation of human lamina propria mononuclear cells in inflammatory bowel disease

Advances in Mucosal Immunology ◽

10.1007/978-94-009-1848-1_209 ◽

1990 ◽

pp. 675-680 ◽

Cited By ~ 2

Author(s):

S Scheiber ◽

G S Nash ◽

S Schloemann ◽

M Bertovich ◽

J Gamero ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Lamina Propria ◽

Bowel Disease ◽

Mononuclear Cells ◽

Lamina Propria Mononuclear Cells ◽

Inflammatory Bowel

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Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms20143574 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3574 ◽

Cited By ~ 4

Author(s):

Hye-Sun Lim ◽

Yu Jin Kim ◽

Bu-Yeo Kim ◽

Soo-Jin Jeong

Keyword(s):

Mrna Expression ◽

P38 Mapk ◽

Inflammatory Responses ◽

Mitogen Activated Protein Kinase ◽

Enzyme Linked Immunosorbent Assay ◽

Mice Model ◽

Tnf Α ◽

Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

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Generation of FOXP3+ Inducible Regulatory T Cells by Lamina Propria Mononuclear Cells in Inflammatory Bowel Disease

Gastroenterology ◽

10.1016/s0016-5085(11)62043-x ◽

2011 ◽

Vol 140 (5) ◽

pp. S-494

Author(s):

Christopher J. Moran ◽

Scott B. Snapper

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Regulatory T Cells ◽

Lamina Propria ◽

Bowel Disease ◽

Mononuclear Cells ◽

Lamina Propria Mononuclear Cells ◽

Inflammatory Bowel

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Zinc Deficiency Activates the IL-23/Th17 Axis to Aggravate Experimental Colitis in Mice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz193 ◽

2019 ◽

Vol 14 (6) ◽

pp. 856-866 ◽

Cited By ~ 4

Author(s):

Yasuki Higashimura ◽

Tomohisa Takagi ◽

Yuji Naito ◽

Kazuhiko Uchiyama ◽

Katsura Mizushima ◽

...

Keyword(s):

Bone Marrow ◽

Lamina Propria ◽

Zinc Deficiency ◽

Mononuclear Cells ◽

Interferon Regulatory Factor ◽

Nuclear Accumulation ◽

Regulatory Factor ◽

Colonic Inflammation ◽

Interferon Regulatory Factor 5 ◽

Lamina Propria Mononuclear Cells

Abstract Background and Aims Patients with inflammatory bowel disease [IBD], especially Crohn’s disease, often develop zinc deficiency. However, the precise mechanisms by which zinc deficiency affects IBD pathology, particularly intestinal macrophage function, remain unclear. We studied the effects of zinc deficiency on the development and progression of colitis in mice. Methods To induce colitis, mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Rag1−/− mice were then given injections of naïve CD4+CD62L+ T cells. The respective degrees of mucosal injury of mice that had received a zinc chelator (TPEN; N,N,N′,N′-tetrakis [2-pyridylmethyl]ethylenediamine) and of control mice were subsequently compared. Colonic lamina propria mononuclear cells were isolated by enzymatic digestion and were examined using flow cytometry. To generate mouse bone marrow-derived macrophages [BMDMs], bone marrow cells were stimulated with mouse macrophage-colony stimulating factor. Results Zinc deficiency aggravates colonic inflammation through the activation of type 17 helper T [Th17] cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory [M1] macrophages in colonic lamina propria mononuclear cells obtained from inflamed colon. Interferon-γ plus lipopolysaccharide-mediated M1 skewing alters the expression of zinc transporters in BMDMs and thereby decreases the intracellular free zinc. TPEN treatment mimicking the effects of the M1 skewing up-regulates IL-23p19 expression, which is strongly related to Th17 development. Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is closely involved in IL-23p19 induction in zinc-deficient macrophages. Conclusions Zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis. This activation is controlled by subcellular distribution of interferon-regulatory factor 5.

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TLR2 affects CD86 expression and inflammatory response in burn injury mice through regulation of p38

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0210 ◽

2017 ◽

Vol 95 (5) ◽

pp. 549-555 ◽

Cited By ~ 2

Author(s):

Li Li ◽

Gang Xu ◽

Chenwang Duan

Keyword(s):

Inflammatory Response ◽

Burn Injury ◽

Vital Role ◽

Mutant Type ◽

Tissue Samples ◽

Tlr2 Agonist ◽

P38 Inhibitor ◽

Tnf Α ◽

Hematoxylin And Eosin

The aim of this study was to assess the effects of TLR2–p38–CD86 signaling pathways on the inflammatory response in a mouse model of burn injury. Wild-type (TLR2+/+) and mutant-type (TLR2−/−) mice were obtained, and a mouse burn injury model was constructed. Tissue samples were examined with hematoxylin and eosin staining and the transferase mediated nick end labeling (TUNEL) method. Macrophages were treated with TLR2 agonist and p38 inhibitor. The expression levels of TLR2, p38, CD86, IL-1β, and TNF-α were quantified by RT-qPCR, Western blot, and ELISA. When compared with the sham group, the burn group had a significantly higher rate of apoptosis as well as higher expressions of TLR2, p38, CD86, IL-1β, and TNF-α. Inhibiting TLR2 was shown to significantly reduce the expressions of p-p38, CD86, IL-1β, and TNF-α. In the results of in-vitro experiments, TLR2 agonist increased the expression of p-p38, CD86, IL-1β, and TNF-α, whereas a p38 inhibitor was shown to reduce the expression of CD86, IL-1β, and TNF-α. Our results suggest that the TLR2–p38–CD86 signaling pathway plays a vital role in inflammation associated with burn injury.

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