The progesterone-induced blocking factor modulates the balance of PKC and intracellular Ca.
OBJECTIVE
Progesterone-induced blocking factor (PIBF) induces Th2 biased cytokine production; therefore, this study investigates the effects of PIBF on the protein kinase C (PKC)/Ca(++) system - which plays a key role in Th1/Th2 differentiation.


METHODS
Proteins from PIBF-treated cells were reacted on Western blots with phospho-specific antibodies recognizing different PKC izoforms. Intracellular free calcium was measured by flow cytometry.


RESULTS
Both interleukin (IL)-4 and PIBF induced PKC phosphorylation, which was abrogated by anti-IL-4Ralpha or anti-PIBF immunoglobulin G pre-treatment. PIBF treatment did not alter intracellular Ca(++) levels. Inhibition of PKCzeta or PKCtheta phosphorylation, but not that of PKCalpha/beta resulted in the loss of STAT6 and Jak1 phosphorylation by PIBF.


CONCLUSIONS
Our data show that PIBF phosphorylates PKC via binding to the IL-4R, without affecting intracellular Ca(++). Phosphorylation of PKCzeta and PKCtheta is required for Jak1 and STAT6 activation, whereas PKCalpha/beta is not involved. These findings explain the mechanism by which PIBF supports a Th2 dominant cytokine pattern.
Kozma
Noemi
N
Department of Medical Microbiology and Immunology, Medical School, Pecs University, Pecs, Hungary.
Halasz
Melinda
M
Palkovics
Tamas
T
Szekeres-Bartho
Julia
J
D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D053613:Janus Kinase 1; D008214:Lymphocytes / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011257:Pregnancy Proteins / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000737:chemistry; D050800:STAT6 Transcription Factor / Q000378:metabolism; D013491:Suppressor Factors, Immunologic
C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D013491:Suppressor Factors, Immunologic; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D011493:Protein Kinase C; D002118:Calcium