Teruko Honda

Inherent potential for production of tumor necrosis factor-α by human intestinal macrophages

Background and aimsTumor necrosis factor (TNF) production by the macrophages in intestines appears to play a critical role in the pathogenesis of Crohns disease (CD). However, it is reported that resident intestinal macrophages (both colonic and small-bowel) do not produce TNF after lipopolysaccharide (LPS) stimulation. It has not yet been proven whether or not intestinal macrophages have an inherent potential to produce TNF. The purpose of this study is to answer this question.Materials and methodsColonic macrophages were isolated from lamina propria of human large intestine and stimulated with a variety of substances: LPS, a lipid A derivative (ONO-4007), killed Streptococcus bacterial body (OK-432), phorbol 12-myristate 13-acetate, and lectins (pokeweed mitogen and Sarcophaga lectin).ResultsColonic macrophages were phenotypically negative for CD14 and positive for CD68 and produced very little TNF in response to LPS, as reported previously. Of the substances tested, only Sarcophaga lectin, which is a defense protein of fleshflies (Sarcophaga peregrina), induced TNF production by the intestinal macrophages. In addition, when the colonic macrophages were cultured on immunoglobulin-A-coated dishes, their characteristic response to LPS was altered, and they produced TNF at a level 6.6 times higher than when on collagen-coated dishes.ConclusionColonic macrophages have an inherent ability to produce TNF. Activation of colonic macrophages by unknown substances may contribute to the induction of TNF production, which causes the intestinal inflammation of CD.

Lipopolysaccharide-treated Human MonocytesRegulate Gene Expressions After Interactionswith Human Adipocytes

Introduction: Monocytes infiltrate tissues and differentiate into tissue-specific macrophages by interaction with other cells in tissues. Macrophages in the arterial wall uptake of oxidized LDL and form foam cells and induce inflammatory changes in tissues by secreting inflammatory cytokines. Chronic inflammation is believed to be involved in the development of cancer and lifestyle-related diseases. Whereas, in human monocytes, the mRNA expression of inflammatory factors increases by interactions with cancer cells, however, this increase can be suppressed by pretreatment with low-dose LPS. In the present study, we investigated changes in the gene expression of some key cytokines, inflammatory factors [IL-1 and adiponectin] and a chemotactic factor [MCP-1], after interactions between human adipocytes and LPS-pretreated human monocytes. Materials and Methods: The human monocyte cell line THP-1 was treated with LPS and subsequently co-cultured with human adipocytes using an insert co-culture system. The gene expressions of inflammatory factors and chemotactic factor were analyzed using quantitative real-time PCR and DNA microarray. Results: The increased mRNA expression of IL-1 β in human adipocytes after co-culture was suppressed by interaction with LPS-pretreated THP-1 cells. The decreased mRNA expression of adiponectin in human adipocytes after co-culture was increased by interaction with LPS-pretreated THP-1 cells. In addition, the increased mRNA expression of MCP-1 in THP-1 cells after interaction with human adipocytes was suppressed by LPSpretreatment. Conclusion: LPS-pretreated human monocytes may have anti-inflammatory effect in adipose tissues. LPS-treated human monocytes may be beneficial for the prevention of diseases caused by chronic inflammation.