Oral and skin keratinocytes are stimulated to secrete monocyte chemoattractant protein‐1 by tumour necrosis factor‐α and interferon‐γ

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC subfamily of chemokines. It is chemoattractant for monocytes, activated memory T cells and dendritic cells. We studied MCP-1 mRNA and protein production in cultured human oral keratinocytes (OK) and skin keratinocytes (SK). MCP-1 production was undetectable in resting keratinocytes. However, stimulation with tumour necrosis factors (TNF-alpha) or interferon-gamma (IFN-gamma) induced MCP-1 mRNA and protein synthesis in both cell types. Together, TNF-alpha and IFN-gamma acted synergistically to increase MCP-1 production. In each case MCP-1 production was greater for SK than OK. The kinetics of IFN-gamma-induced MCP-1 production were similar for both cell types, peaking around 72 h. In contrast, TNF-alpha induced a more rapid increase in MCP-1 production by SK than OK, peak production occurring after 24 and 72 h, respectively. IL-1alpha and IL-4 did not induce MCP-1 production. However, in combination with IFN-gamma, they induced a small extra increase in MCP-1 production in SK but not OK.

Resident Cell Chemokine Expression Serves as the Major Mechanism for Leukocyte Recruitment During Local Inflammation

“…The importance of this process is underscored by the fact that defects in leukocyte recruitment can lead to a state of immunosuppression (37,38). As the various mechanisms of leukocyte recruitment are identified, it is becoming clear that the dynamic event of cell migration is not restricted to leukocyte-endothelial cell interactions, but is directed in large part by cells that comprise the resident tissue in the inflamed area, including stromal, epithelial, and endothelial cells (23)(24)(25)39). Data from the set of studies contained in this investigation demonstrate that resident tissue cells are a significant component of the initial localized in vivo response, a reaction that is dictated by the sequence of cytokine-chemokine expression.…”

“…A number of in vitro studies have shown that both resident cells (23)(24)(25) and leukocytes (26 -28) may synthesize chemokines after stimulation by proinflammatory cytokines. However, the contribution of resident cells vs recruited leukocytes in the evolution of an acute inflammatory event in vivo is not clear, as increasing evidence suggests that resident, structural cells in the tissue may play a key effector role during inflammation via chemokine synthesis (reviewed in Ref.…”

Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

“…The proximity of infiltrating T-cells and epithelium in OLP, which sometimes facilitates interactions between T-cells and epithelium, suggests CD40 and CD154 ligation in OLP. This ligation induces or enhances multiple effects in epithelial cells, including increasing the production of proinflammatory cytokines (5,28) and chemokines (5,(29)(30)(31). Increased production of these molecules in the epithelial area in OLP likely increases inflammation.…”

“…Specifically, increased expression of CXC-ELR-chemokines in OLP is due in part to ligation of CD40 on oral epithelial cells, as was shown previously in cervical carcinoma cells (26). Furthermore, increased production of RANTES by keratinocytes in OLP (32) might be influenced by CD40 ligation (29,33).…”

CC and CXC Chemokines Patterns in Psoriasis Determined by Protein Array Method Were Influenced by Goeckerman’s Therapy

“…The list of such biologically active compounds is impressive and includes, amongst others, pluripotent proinflammatory cytokines e.g. TNFα; IL-8 and other chemokines, and growth factors VEGF and bFGF (23,28,30).…”