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Table 1 Effect of 5-HT7 receptor signaling on different immune cells and inflammatory conditions

From: Role of 5-HT7 receptors in the immune system in health and disease

Cell Type

5-HT7 Effect

Dendritic cells

Induces secretion of IL-1β and IL-8; reduces secretion of IL-12 and TNF-α

Induces process branching and elongation

Monocytes, Macrophagues, Microglia

Pro- and anti-inflammatory

Anti-apoptotic

Increase in TNF-α, IL-6, Bcl-6, NF-kB

AS-19 (agonist) decreases IL-12, TNF-α, and type 1 interferons; enhances production of TGF-β1

SB-269970 (antagonist) increases TNF-α and IL-12

Lymphocyte

Concanavalin A, reserpine, and physical restrain increased expression of 5-HT7

Increase in proliferation rate, expression of CD25

Disease Model

5-HT7 Effect

Inflammatory Bowel Disease

5-HT7 expression increased in DSS-induced colitis

5-HT7 blockade/ablation results in increased severity of acute and chronic colitis

5-HT7 agonists have anti-inflammatory effect

Lung Injury

5-HT7 antagonists decrease lung fluid content, TNF-α, IL-6, oxidative stress in bleomycin-induced lung injury

5-HT7 antagonists reduce collagen deposition, expression of TGF-β1 and procollagen type Ӏ

Central nervous system inflammation

LP-211 (agonist) reduces neurotoxic effect of β-amyloid in a model of Alzheimer disease

AS-19 (agonist) reduces pro-apoptotic effect of streptozotocin

Sepsis

In LPS-induced sepsis, 5-HT7 mRNA increases in parallel to TNF-α, IL-1β, NF-κB

LP-44 (agonist) attenuates cell injury and reduces iNOS and TNF-α

In a CLP-induced sepsis, AS19 increases survival; reduces tissue injury, inflammatory cytokines, lung NF-κB

Liver Injury

5-HT7 signaling induced during chronic liver injury

Reduced ALT and AST levels

Increased superoxide dismutase

Reduced TNF-α, IL-6, TGF-β1

Soft tissue inflamation

In carrageenan-induced paw inflammation, 5-HT7 agonists reduce cyclooxygenase mRNA expression; decrease oxidative stress, serum cytokine levels