PMID- 7600258
OWN - NLM
STAT- MEDLINE
DCOM- 19950807
LR  - 20191031
IS  - 0742-2091 (Print)
IS  - 0742-2091 (Linking)
VI  - 11
IP  - 1
DP  - 1995 Feb
TI  - Chemical induction of interleukin-8, a proinflammatory chemokine, in human 
      epidermal keratinocyte cultures and its relation to cytogenetic toxicity.
PG  - 37-50
AB  - Tumor promoters, proinflammatory cytokines, endotoxins, and protein synthesis 
      inhibitors can modulate cell cycle kinetics of various cell types, stimulate 
      production of reactive oxygen species, and induce keratinocytes to produce 
      interleukin-8 (IL-8), a potent chemotactant for polymorphonuclear neutrophils and 
      T lymphocytes. The aim of this study was to determine whether perturbations of 
      cytogenetic responses correlated with the induction of IL-8 expression. Cultures 
      of primary human keratinocytes were grown in serum-free medium with 5 mumol/L 
      bromodeoxyuridine to label DNA and exposed either to 
      phorbol-13-myristate-12-acetate (PMA) (0.0001-100 ng/ml), cycloheximide (CHX) 
      (0.01-50 micrograms), lipopolysaccharide (0.1-100 micrograms/ml), tumor necrosis 
      factor-alpha (TNF alpha) (3.13-50 ng/ml), or interleukin-1 alpha (IL-1 alpha) 
      (1-182 pg/ml). Metaphase chromosome preparations were stained by a 
      fluorescence-plus-Giemsa technique to differentiate sister chromatids. For IL-8 
      production, keratinocytes were grown to 70% confluency and then exposed to 
      chemicals for 24 h. Immunoreactive IL-8 was quantitated from the supernatants by 
      ELISA. With the exception of benzo(a)pyrene used as a positive control, none of 
      the agents induced sister chromatid exchanges. However, PMA and TNF alpha induced 
      IL-8 production that coincided with significant cell cycle inhibition. IL-1 alpha 
      had no effect on cytogenetic endpoints, yet stimulated a 6.3-fold increase in 
      IL-8. CHX inhibited cell cycle progression and mitotic activity at concentrations 
      that were 200 times lower than required for IL-8 induction; however, puromycin 
      (0.31-10 micrograms/ml), another protein synthesis inhibitor, did not induce 
      IL-8. At all concentrations tested, TNF alpha reduced the mitotic index by 
      approximately 45%, slowed cell cycle progression by approximately 3.5 h, and 
      induced a flat, albeit large, IL-8 response at concentrations > or = 12.5 ng/ml. 
      These agent-specific response patterns suggest that induction of IL-8 production 
      is not always the inevitable result of cell cycle perturbations or genetic 
      damage.
FAU - Wilmer, J L
AU  - Wilmer JL
AD  - National Institute of Environmental Health Sciences, Environmental Immunology and 
      Neurobiology Section, Research Triangle Park, North Carolina, USA.
FAU - Luster, M I
AU  - Luster MI
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Cell Biol Toxicol
JT  - Cell biology and toxicology
JID - 8506639
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phorbol Esters)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 98600C0908 (Cycloheximide)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Bromodeoxyuridine
MH  - Cell Cycle/drug effects
MH  - Cells, Cultured
MH  - Culture Media, Serum-Free
MH  - Cycloheximide/pharmacology
MH  - DNA Damage/drug effects
MH  - Epidermis/metabolism
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Interleukin-8/*biosynthesis
MH  - Keratinocytes/drug effects/*metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Metaphase
MH  - Phorbol Esters/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
AID - 10.1007/BF00769991 [doi]
PST - ppublish
SO  - Cell Biol Toxicol. 1995 Feb;11(1):37-50. doi: 10.1007/BF00769991.