Curcumin Attenuates TNF‐α‐induced Expression of Intercellular Adhesion Molecule‐1, Vascular Cell Adhesion Molecule‐1 and Proinflammatory Cytokines in Human Endometriotic Stromal Cells

Abstract

Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has long been used in folk medicine as an antiinflammatory remedy in Asian countries. Endometriosis is a chronic gynecological inflammatory disorder in which immune system deregulation may play a role in its initiation and progression. A number of mediators, including cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); proinflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6 and IL-8; and chemokines such as monocyte chemotactic protein-1 (MCP-1), play key roles in the pathogenesis of endometriosis. The aim of our study was to explore the effect of curcumin on the expression of these critical molecules in human ectopic endometriotic stromal cells isolated from women with endometriosis. Endometriotic stromal cells treated with curcumin showed marked suppression of TNF-α-induced mRNA expression of ICAM-1 and VCAM-1. Curcumin treatment also significantly decreased the TNF-α-induced cell surface and total protein expression of ICAM-1 and VCAM-1 in a dose-dependent manner. In addition, treatment of endometriotic stromal cells with curcumin markedly inhibited TNF-α-induced secretion of IL-6, IL-8 and MCP-1. Furthermore, curcumin inhibited the activation of transcription factor NF-κB, a key regulator of inflammation, in human endometriotic stromal cells. These findings suggest that curcumin may have potential therapeutic uses in the prevention and treatment of endometriosis.

The Complementary and Alternative Medicine for Endometriosis: A Review of Utilization and Mechanism

“…Some studies discovered that the number of microvessels and the protein expression of VEGF were decreased in the ectopic endometrium of rat EM models with Curcumin treatment [79], and the mRNA expression of the tumor necrosis factor- α -induced (TNF- α -induced) cell surface and total protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were decreased. Additionally, the secretion of IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) was decreased and the activation of transcription factor NF- κ B was suppressed in human endometriotic stromal cells with Curcumin treatment [80]. Some other studies showed that the expression and activities of matrix metalloproteinase (MMP)-2 [81], MMP-3 [82], MMP-9 [83], and VEGF [84] protein were inhibited in rat EM models that received Curcumin treatment, and the endometriotic lesions were reduced.…”

Interplay between Misplaced Müllerian-Derived Stem Cells and Peritoneal Immune Dysregulation in the Pathogenesis of Endometriosis

“…A substantial body of evidence suggests that a large number of mediators, including cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106) [137] as well as proinflammatory cytokines such as TNF- α , IL1, IL6, and IL8, and chemokines such as MCP-1, play key roles in the pathogenesis of endometriosis. These factors are present in PF as well as in endometriotic implants, and TNF- α in particular is regarded as a critical regulatory molecule in eliciting inflammatory immune responses in endometriosis [138].…”

“…These data suggest that there may be cross-talk between endometrial stromal cells and leukocytes in normal as well as in endometriotic endometrium and peritoneal fluid via ICAM-1 and its receptors. Furthermore, significantly increased ICAM-1 expression in ectopic endometrial stromal cells from endometriomas is enhanced by stimulation with proinflammatory cytokines such as IL-1 β and IFN- γ , indicating the important role of peritoneal cytokine milieu in the regulation of ICAM-1 expression in endometriotic stromal cells and consequently in the pathogenesis of endometriosis [137]. In addition to ICAM-1, VCAM-1 is also expressed in human endometrial stromal cells.…”

Curcumin improves the integrity of blood–spinal cord barrier after compressive spinal cord injury in rats

“…Inflammatory factors have been shown to increase BSCB permeability by timedependently modulating the expression and distribution of tight junction (TJ) proteins [11,12]. Cur, which is a naturally occurring potent inducer of HO-1 [13,14], provides protection against the release of inflammatory factors [15]. Recently, Cur has been demonstrated to protect human intestinal epithelial cells against the H 2 O 2 -induced disruption of TJ and barrier dysfunction through the HO-1 pathway [10].…”