Curcumin ameliorates TNF-α-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells

Abstract

Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes into the site of inflammation. In this study, we investigated the inhibitory effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its underlying action mechanism in the TNF-α-stimulated keratinocytes. Curcumin induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent manners in the HaCaT cells. Curcumin suppressed TNF-α- induced ICAM-1 expression and subsequent monocyte adhesion, which were reversed by the addition of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory effect of curcumin on the TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that curcumin may exert its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes. [BMB Reports 2013;46(8): 410-415]

Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes

“…In the present study, we confirmed that phloretin suppressed the TNF-α-induced translocation of NF-κB into the nucleus, thereby suppressing IL-6, IL-8, MCP-1, MDC, and TREC expression. Previous studies had found that inhibited PI3K-Akt signaling could suppress NF-κB movement into the nucleus in HaCaT cells [7,35]. The MAPK pathways also are important regulatory factors in promoting NF-κB activation [8].…”

“…Previous studies found that the surface of inflammatory epidermal keratinocytes could express cell adhesion molecules to bind and adhere to infiltrating lymphocytes in the lesional skin of patients with atopic dermatitis [7]. In the lesional skin, infiltrating neutrophils and monocytes could release inflammatory mediators and cause severe skin lesions [31].…”

“…The NF-κB, containing the p50 and p65 subunits, can exist in an inactive state in the cytoplasm through the suppressive effects of an inhibitor, inhibitor of nuclear factor kappa B (IκB), and in the cytoplasm of unactivated keratinocytes. Stimulation of the keratinocytes by TNF-α can open inflammatory signaling pathways and stimulate the phosphorylation of IκB which then results in the entry of NF-κB into the nucleus to activate the expression of inflammatory mediator genes [7]. In addition, inflammatory keratinocytes may also stimulate activation of the mitogen-activated protein kinase (MAPK) pathways to assist and cause an even more severe inflammatory response [8].…”

“…Hence, if the NF-κB and MAPK pathways were suppressed, there may be a decrease in the inflammatory response in relevant skin diseases. Inflammatory keratinocytes also express adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), that promote adsorption of leukocytes into skin tissue [7]. In the inflammatory epidermis, ICAM-1 plays a critical role to cause the inflammatory response in the interaction between leukocytes and keratinocytes.…”

Synergistic effects of combined curcumin and antibiotic in ameliorating an animal model of Helicobacter pylori infection

“…Turmeric is a medical plant which is widely used as edible seasoning from its rhizome. Rhizome extract is called curcuminoid and it includes curcumin, dimetixocorquine and dimetixine curcumin base [10]. Curcumin is insoluble in water and ether but dissolves in alcohol, acetic acid, alkaline and some oils, including olive oil.…”