Secretion of Bovine Uterine Proteins in Response to Type I Interferons1

Bovine interferon-tau (bIFN-τ) is secreted by the developing conceptus and initiates antiluteolytic events by interacting with uterine membrane receptors. We have identified three endometrial proteins (~ 8, 16, and 28 kDa; P8, P16, and P28; respectively) that are secreted in response to recombinant (r) bIFN-τ. The objective of this study was to determine whether or not secretion of these proteins was a unique response to IFN-τ during early pregnancy. Three experiments were designed to examine secretion of endometrial proteins as a function of time in culture (0, 3, 6, 12, 18, 24 h), stage of the estrous cycle and pregnancy (Days 15, 18, 0/21), and dose of Type I IFN (0, 0.5, 5, and 25 nM; rbIFN-τ, rbIFN-α, and roIFN-τ). Endometrium was cultured for times specified with L-[3H]leusine to generate radiolabeled proteins. Secreted proteins were quantitated by using one-dimensional (1D)-PAGE, fluorography, and densitometry. Secretion of P8, P16, and P28 increased over time (p < 0.0001) in culture and in response to 25 nM rbIFN-τ (p < 0.05). Secretion of P8 in response to rbIFN-τ was higher (p < 0.05). Secretion of P8 in response to rbIFN-τ was higher (p < 0.0005) in endometrium collected from pregnant than nonpregnant heifers, but did not differ across the days examined. Although secretion of P8 was higher (p < 0.0001) in the presence than in the absence of rbIFN-τ, it was not affected by rbIFN-α. Secretion of P16 was higher (p < 0.0001) in endometrium collected from pregnant than from nonpregnant heifers, but did not differ across the days examined. Both rbIFN-τ and rbIFN-α stimulated (p < 0.0005) secretion of P16, but this effect was significant only in tissues collected during the estrous cycle. Pregnancy status, day of collection, and treatment with rblFN-α did not affect secretion of P28. However, rbIFN-τ stimulated (p < 0.001) secretion of P28. Dose-response studies revealed that secretion of P8 and P28 was stimulated in a dosedependent manner only by rbIFN-τ (p < 0.005). Secretion of P16 was stimulated by all Type I IFNs examined (p < 0.01). These data may be interpreted to mean that the endometrium has the ability to distinguish between closely related Type I IFNs.