Isolation and bioactivities of three IL-1 beta N-terminal variants.
Three distinct N-terminal variants of rhIL-1 beta can be generated by expression of the IL-1 beta gene in E. coli; the naturally occurring Ala1 species, Met0-Ala1 and des-Ala1 proteins. Since most studies with rhIL-1 beta have used a mixture of two or more variants, we have evaluated their individual bioactivities. The variants were resolved by cation exchange HPLC. Bioactivity measurement on murine thymocytes gave a potency order of Ala1 greater than des-Ala1 greater than Met0-IL-1 beta. Analysis using human T-cells co-stimulated with PMA showed a potency order of Ala1 greater than des-Ala1 greater than Met0-IL-1 beta. Thus changes in the N-terminal amino acid of IL-1 beta changes the activity of the protein. Since murine and human T-cells respond similarly, the interactions between the N-terminus of rhIL-1 beta and their receptors probably occur through comparable mechanisms.
Richard
K A
KA
Department of Hypersensitivity Diseases, Upjohn Company, Kalamazoo, MI 49001.
Yem
A W
AW
Deibel
M R
MR
Staite
N D
ND
D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects
D007375:Interleukin-1; D011994:Recombinant Proteins