title: Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells.
abstract: OBJECTIVE
  The habit of khat chewing has been associated with increased risk of systemic and oral disease. Although research has been conducted on the affects of khat on oral epithelial cells, little is known about its influence on immune cells. This study examined the biological effects of khat on the phenotype and function of peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  Khat-stimulated PBMCs were examined for signs of cytotoxicity, apoptosis and changes in cell surface receptor and cytokine expression. Khat-induced regulation of transcription factors and stress-related factors were examined, as was PBMC phagocytic activity against oral bacteria.
  
  
  RESULTS
  Khat was cytotoxic to PBMC in a dose- and time-dependent manner and cell death was mediated by apoptosis. Khat-treated PBMC showed increased expression of co-stimulatory molecules (CD80, CD86 and MHC II) and pattern recognition receptors (TLR-2, TLR-4 and TREM-1) but secretion of inflammatory cytokines (TNFα, IL-6, CCL5, CXCL8) was inhibited. In contrast, khat induced an increase in the anti-inflammatory cytokine IL-10 as well as IL-2, IFN-γ, FasL and HSP70. These khat-induced alterations were accompanied by increased expression of transcription factors p38 MAPK and HIF-1α, whilst expression of NFκB p65 was inhibited. Although the ability of PBMC to phagocytose dextran and oral bacteria was inhibited, production of reactive oxygen species was increased.
  
  
  CONCLUSIONS
  These data suggest that khat may severely influence the effectiveness of immune surveillance and anti-microbial capacity of PBMCs.
authors: Academic Unit of Oral & Maxillofacial Medicine & Surgery, School of Clinical Dentistry, University of Sheffield, Sheffield, UK. c.murdoch@sheffield.ac.uk
authors: Craig
authors: C
authors: Murdoch
authors: Hesham Abdul
authors: HA
authors: Aziz
authors: Hsin-Yu
authors: HY
authors: Fang
authors: Hussun
authors: H
authors: Jezan
authors: Raga
authors: R
authors: Musaid
authors: Munitta
authors: M
authors: Muthana
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D029754:Catha; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008562:Membrane Glycoproteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C408842:TREM1 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D048051:p38 Mitogen-Activated Protein Kinases