ABSTRACT
AIMS OF STUDY: 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). MATERIAL AND 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. CONCLUSION: These data suggest that khat may severely influence the effectiveness of immune surveillance and anti-microbial capacity of PBMCs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Catha , Leukocytes, Mononuclear/drug effects , Plant Extracts/pharmacology , Anti-Bacterial Agents/toxicity , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Cytokines/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Leukocytes, Mononuclear/metabolism , Membrane Glycoproteins/metabolism , Phagocytosis/drug effects , Phenotype , Plant Extracts/toxicity , Plant Leaves/chemistry , Reactive Oxygen Species/metabolism , Receptors, Immunologic/metabolism , Streptococcus/drug effects , Streptococcus/growth & development , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Transcription, Genetic/drug effects , Triggering Receptor Expressed on Myeloid Cells-1 , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
Proliferative activity of cerebellar juvenile pilocytic astrocytomas (CJPA) and its significance for prognosis was retrospectively investigated. Forty-four consecutive children operated between 1981 and 1997 with a mean age of 8.3 years (3 months to 20 years) were reviewed. Clinical and radiological follow-up was available for 38 patients ranging from 0 to 18 yrs (mean 6.3 years). Proliferative activity was determined by MIB-1 immunohistochemistry on sections of resected tumor specimen. Total resection was achieved in 35 children (79.5%), subtotal in 9 (20.5%). Currently, 31 are tumor-free, 6 have stable remnants, one developed spinal seeding and one died. Radiology revealed a cystic mural node type tumor in 27 patients (61.4%), a solid lesion with a small cyst in 5 patients (11.4%), and a solid tumor in 12 patients (27.3%). Mean MIB-1 labeling index (LI) of all tumors was 4.4% (range 0.6-12%, SD = 2.7) and did not correlate with age, gender, localization, amount of resection, follow-up status, histological appearence or grade of neovascularization, but showed a significant correlation to radiological types: 6.9% in solid tumors versus 3.7% in the cystic mural node type (p = 0.0037). Five year progression-free survival (PFS) of all patients was 84.4%, differences between subgroups of MIB-1 <5% (27 patients, PFS = 87.4%) and MIB-1 >5% (13 patients, PFS = 76.3%) were not significant. CJPA showed a remarkable high MIB-1 LI, but no significant correlation to PFS in this series. Nevertheless, radiologically solid tumors demonstrated a significantly higher MIB-1 LI and thus may need further investigation for possible increased ability of regrowth.
