Enhanced interferon-gamma production and B7-2 expression in isolated intestinal mononuclear cells from patients with

M Noguchi1, N Hiwatashi, Z Liu

  • 1Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

Insights

Interferon-gamma (IFN-gamma) levels and B7-2 expression are elevated in Crohn's disease intestinal tissues. This suggests a mechanism involving IFN-gamma and B7-2 in amplifying inflammatory responses in Crohn's disease.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Interferon-gamma (IFN-gamma) plays a role in inflammatory bowel disease (IBD), but its significance is debated.
  • IFN-gamma is known to upregulate B7-2 costimulatory molecules on monocytes.

Purpose of the Study:

  • To investigate IFN-gamma production and B7-2 expression in the intestinal mucosa and lamina propria mononuclear cells (LPMC) of patients with Crohn's disease (CD) and ulcerative colitis (UC).
  • To explore the role of IFN-gamma in modulating B7-2 expression on LPMC.

Main Methods:

  • Measurement of IFN-gamma levels in intestinal mucosa and isolated LPMC from CD, UC patients, and controls.
  • Flow cytometry analysis to assess B7-2 expression on LPMC.
  • Incubation of CD LPMC with endotoxin to evaluate B7-2 induction.

Main Results:

  • Mucosal IFN-gamma production was significantly higher in CD patients compared to controls, but not in UC patients.
  • Both IFN-gamma production and B7-2 expression were elevated in LPMC from CD patients relative to UC patients and controls.
  • Endotoxin stimulation further enhanced B7-2 expression on LPMC from CD patients.

Conclusions:

  • Elevated IFN-gamma production and B7-2 expression in the intestinal mucosa of CD patients suggest a specific role for this pathway in the disease.
  • The induction of B7-2 on LPMC by IFN-gamma may contribute to the amplification of T cell proliferation and lymphokine production in CD.

Related Concept Videos

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel Disease...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...
Inflammatory Bowel Disease II: Crohn's Disease01:30

Inflammatory Bowel Disease II: Crohn's Disease

Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...