Search

Effects of interferon-β (IFN-β) on the gene expressions occurring in vitro in mouse spleen cells after the treatment with concanavalin A (Con A) were examined by Northern analysis. The results show that IFN-β strongly suppressed the induction of IFN-γ mRNA transcription and, interestingly, profoundly decreased the steady-state level of the T-cell receptor β-chain (TCRβ) gene mRNA without any substantial effect on some other gene expressions, such as those of the interleukin-2 (IL-2) and the major histocompatibility complex (MHC) class I genes. These indicate that although the IFN-γ and IL-2 genes are co-induced by Con A stimulation, only the former is specifically susceptible to the inhibitory effect of 1FN-β. Moreover, the expression of the TCRβ gene was suppressed by IFN-β under Con A stimulation, suggesting that IFN-β might work as a negative regulator in immune recognition by activated T cells. [ABSTRACT FROM AUTHOR]

Murine peritoneal macrophages pretreated with interferon (IFN)-α and then stimulated by opsonized zymosan produced two to three times more LTB4 than untreated macrophages. However, PGE2 production was not changed by IFN-α. Meanwhile, IFN-γ did not affect the production of LTB4 and PGE2. From the results it is considered that IFN-α can modulate inflammation or host defence through the production of LTB4. [ABSTRACT FROM AUTHOR]

Background: Patients with cancer are treated with chemotherapeutics that cause adverse effects, including erectile dysfunction (ED)., Objectives: We investigated erectile function in rats after the administration of anticancer agents based on data retrieved through mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database., Materials and Methods: The statistical signal strength for the association between anticancer drugs and ED was calculated using the reporting odds ratio (ROR). A drug-event combination was detected when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1.00. Rats were administered anticancer agents detected in the FDA AERS analysis. Erectile function was assessed using intracavernous pressure (ICP) and mean arterial pressure (MAP) analysis after electrical stimulation of the cavernous nerve. Statistical significance was determined using Welch's t-test or two-way ANOVA., Results: Melphalan (L-PAM; ROR = 4.72, 95% CI = 2.78-8.00), vincristine (VCR; ROR = 2.47, 95% CI = 1.54-3.97), docetaxel (DTX; ROR = 2.25, 95% CI = 1.28-3.95), methotrexate (MTX; ROR = 1.96, 95% CI = 1.39-2.75), and doxorubicin (DOX; ROR = 1.82, 95% CI = 1.07-3.19) enhanced ED risk. L-PAM and MTX decreased the ICP/MAP ratio 1 week after administration. VCR and DOX decreased erectile function 4 weeks after administration. DTX decreased erectile function at all assessed time points., Discussion and Conclusion: Certain anticancer agents should be considered risk factors for ED. Our results provide possible treatment strategies for maintaining erectile function in cancer survivors, including careful erectile function monitoring after treatment., (© 2021 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

A monoclonal antibody to human interferon-alpha, termed HT-1 antibody, with a broad reactivity to various subtypes of interferon-alpha was prepared. It bound and neutralized all of the four subtypes of E. coli-derived human recombinant interferon-alpha (alpha 1, alpha 2, alpha 4, and alpha 6) tested; it also neutralized human natural leukocyte interferon but only partially. Human interferon-beta and -gamma were not bound. The antibody conjugated to Sepharose beads retained over 90% of human leukocyte interferon induced by Sendai virus. The bound interferon was recovered by acid elution in good yields and in almost pure form (specific activity was about 2 X 10(8) international units/mg protein). The purified interferon showed, in SDS-polyacrylamide gel electrophoresis, an activity profile with major peaks in a mol. wt. range of 17,000-22,000, which completely agreed with the profile shown by polyclonal antibody-purified interferon. Such purified leukocyte interferon-alpha preparations containing most of the naturally occurring subtypes can be useful for clinical and other purposes.

A mouse leukemic cell line L1210 Sg with a low sensitivity to interferon-gamma (IFN-gamma) was described. On the nature of the antiviral action and binding of IFN, L1210 Sg cells were compared with L1210 m cell line which is sensitive to IFN-gamma. For a half reduction of the vesicular stomatitis virus-RNA synthesis, L1210 Sg cells required 500-fold more IFN-gamma than L1210 m cells did. However, both cell lines were induced to the antiviral state to the same extent with IFN-alpha or -beta. L1210 Sg and L1210 m cells were sensitive to the anti-proliferative action of IFN-alpha and -beta, but insensitive to IFN-gamma. (2'-5')Oligoadenylate synthetase was induced in these cell lines by IFN-beta, but not by IFN-gamma, which suggests that the induction of this synthetase may not be responsible for the antiviral action of IFN-gamma. No substantial difference between L1210 Sg and L1210 m cells was found in IFN receptors for IFN-gamma and IFN-beta either in number per cell or in their affinity to corresponding IFN type. However, differences were noted in time course profiles of cell-associated IFN-gamma at 37 C: in L1210 m cells, a rise-and-decay profile of IFN-gamma bound to cells was observed at 37 C, but in L1210 Sg cells, rise and slight decay was observed. On the other hand, a similar rise-and-decay curve of IFN-beta bound to these cells was observed. These results indicated that the low sensitivity of L1210 Sg cells to IFN-gamma may be due to this slight decay of receptor-bound IFN-gamma.

In a search for a useful enhancer to control expression of interferon (IFN) gene in mammalian cells, mouse IFN-beta cDNA ligated 3' downstream to the enhancer-promoter of either mouse metallothionein-I (MT-I) or Drosophila heat shock protein (HSP) was introduced into various cultured cells by calcium-phosphate precipitation method, and the level of IFN transiently produced was compared. In the case of the MT-I enhancer-promoter, low levels of IFN were produced without induction (0-21 IU/ml) and the level increased 5-50 times by heavy metals. In contrast, the basal level of expression of the HSP enhancer-promoter was very low and its expression was increased several hundred to thousand times by heat shock or arsenite. Thus the HSP enhancer-promoter appears to be a potent inducible element with very low basal level and high inducibility.

Mouse monoclonal antibodies (mAb) to human interferon-gamma (HuIFN-gamma) were characterized. The mAbs studied--E4-18, G4-15, and SAT-1--which are all IgGl-type, reacted to all HuIFN-gamma molecular species, both glycosylated and non-glycosylated. Affinity constants calculated of E4-18 and G4-15 didn't have considerable differences for both kinds of HuIFN-gamma (1-3 x 10(8) liter/mol), but SAT-1 had a difference--a higher value (10(10) liter/mol) for the former than for the latter (8 x 10(8) liter/mol). In epitope specificity, the results suggested that E4-18 and G4-15 recognized an overlapped region remote from the region of SAT-1. Competition experiment using synthetic peptides suggested that epitope of G4-15 is around N9-26 of the HuIFN-gamma sequence. Those mAbs could be used for sandwich radioimmunoassay of HuIFN-gamma using double mAbs in two combinations, one (G4-15/E4-18) based on dimer forms of HuIFN-gamma and the other (SAT-1/E4-18) based on epitope difference. The mAbs are all neutralizing antibodies in which SAT-1 neutralized at a lower concentration than did G4-15, and at a much lower one than did E4-18. The receptor binding of HuIFN-gamma was inhibited by mAbs G4-15 and SAT-1. Efficacy of G4-15 and SAT-1 for the inhibition correspond with that for neutralization.