Effects of interleukin-1alpha, interleukin-1 receptor antagonist, and neutralizing antibody on proinflammatory cytokine expression by human squamous cell carcinoma lines.
Proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been detected in tumor specimens and primary cell cultures from patients with head and neck squamous cell carcinoma. IL-1alpha has been reported to play an important role in inducing the expression of cytokines IL-6, IL-8, and GM-CSF during inflammation. We examined whether these cytokines are expressed together in five primary and seven established UM-SCC cell lines, and we also examined the effects of IL-1alpha, IL-1 receptor antagonist or neutralizing antibody (Ab) upon expression of this repertoire of proinflammatory cytokines in established UM-SCC lines. Secretion of proinflammatory cytokines IL-1alpha, IL-6, IL-8, and GM-CSF was detected by ELISA in both the primary and established UM-SCC lines. Constitutive expression of specific mRNAs for these cytokines was confirmed in the UM-SCC lines by reverse transcriptase-PCR and Northern blot analysis. Addition of recombinant IL (rIL)-1alpha but not rIL-6 induced a dose-dependent increase in IL-8 and GM-CSF production. IL-1 receptor antagonist (IL-RA) or anti-IL-1 neutralizing Ab could completely inhibit the rIL-1alpha-inducible increase in IL-8 and GM-CSF expression, but the inhibitors had a negligible effect on the constitutive level of production of the cytokines. Transfer and expression of the IL-1alpha gene in a low-cytokine-producing cell line, UM-SCC-38, induced IL-8 and GM-CSF expression, but this expression was also not inhibited by IL-1RA or anti-IL-1 neutralizing Ab. We conclude that IL-1alpha can enhance the expression of cytokines IL-8 and GM-CSF in UM-SCC cell lines but that constitutive expression of these cytokines by UM-SCC is not inhibited by exogenous IL-1RA or neutralizing Ab.
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892, USA.
Z
Z
Chen
I
I
Colon
N
N
Ortiz
M
M
Callister
G
G
Dong
M Y
MY
Pegram
O
O
Arosarena
S
S
Strome
J C
JC
Nicholson
C
C
Van Waes
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor