Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1995 Nov;86(3):469–474.

Cellular distribution of proteasome subunit Lmp7 mRNA and protein in human placentas.

K F Roby 1, Y Yang 1, D Gershon 1, J S Hunt 1
PMCID: PMC1383953  PMID: 8550087

Abstract

Human leucocyte antigen (HLA) class I antigen expression is closely controlled in placental trophoblast cells, which interface directly with genetically disparate maternal blood and tissues during pregnancy. In this study, the possibility that LMP7, a proteasome component that may be required for processing of class I-associated peptides, might be lacking or refractory to cytokine induction in trophoblast cells that fail to display HLA class I antigens was investigated. Analysis of Lmp7 mRNA and protein in paraformaldehyde-fixed placentas by in situ hybridization and immunohistochemistry revealed that both HLA class I-positive and HLA class I-negative trophoblast cells contain Lmp7 gene products. Consistent with these results, northern blot hybridization studies showed that HLA class I-positive (JEG-3) and HLA null (Jar) trophoblast-derived cell lines contain Lmp7 mRNA. After 48 hr of exposure to HLA class I-modulating cytokines, Lmp7 mRNA levels in JEG-3 cells were markedly increased by two interferons (IFN-beta, IFN-gamma) and tumour necrosis factor (TNF) whereas at the same time point, Jar cell Lmp7 mRNA was modestly enhanced by IFN-gamma. Collectively, the findings indicate that expression of HLA class I antigens in trophoblast cells is unlikely to be restricted by lack of Lmp7 gene products and suggest that endogenous placental cytokines may have different influences on Lmp7 mRNA levels in phenotypically distinct trophoblast subpopulations.

Full text

PDF
469

Images in this article

471Figure 2
on p.471
471Figure 3
on p.471
472Figure 4
on p.472

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aki M., Shimbara N., Takashina M., Akiyama K., Kagawa S., Tamura T., Tanahashi N., Yoshimura T., Tanaka K., Ichihara A. Interferon-gamma induces different subunit organizations and functional diversity of proteasomes. J Biochem. 1994 Feb;115(2):257–269. doi: 10.1093/oxfordjournals.jbchem.a124327. [DOI] [PubMed] [Google Scholar]
  2. Akiyama K., Kagawa S., Tamura T., Shimbara N., Takashina M., Kristensen P., Hendil K. B., Tanaka K., Ichihara A. Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by interferon-gamma for acquirement of the functional diversity responsible for antigen processing. FEBS Lett. 1994 Apr 18;343(1):85–88. doi: 10.1016/0014-5793(94)80612-8. [DOI] [PubMed] [Google Scholar]
  3. Akiyama K., Yokota K., Kagawa S., Shimbara N., Tamura T., Akioka H., Nothwang H. G., Noda C., Tanaka K., Ichihara A. cDNA cloning and interferon gamma down-regulation of proteasomal subunits X and Y. Science. 1994 Aug 26;265(5176):1231–1234. doi: 10.1126/science.8066462. [DOI] [PubMed] [Google Scholar]
  4. Bulmer J. N., Morrison L., Johnson P. M., Meager A. Immunohistochemical localization of interferons in human placental tissues in normal, ectopic, and molar pregnancy. Am J Reprod Immunol. 1990 Mar-Apr;22(3-4):109–116. doi: 10.1111/j.1600-0897.1990.tb00652.x. [DOI] [PubMed] [Google Scholar]
  5. Chen H. L., Yang Y. P., Hu X. L., Yelavarthi K. K., Fishback J. L., Hunt J. S. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. Am J Pathol. 1991 Aug;139(2):327–335. [PMC free article] [PubMed] [Google Scholar]
  6. Ciechanover A. The ubiquitin-proteasome proteolytic pathway. Cell. 1994 Oct 7;79(1):13–21. doi: 10.1016/0092-8674(94)90396-4. [DOI] [PubMed] [Google Scholar]
  7. Ellis S. A., Palmer M. S., McMichael A. J. Human trophoblast and the choriocarcinoma cell line BeWo express a truncated HLA Class I molecule. J Immunol. 1990 Jan 15;144(2):731–735. [PubMed] [Google Scholar]
  8. Ellis S. A., Strachan T., Palmer M. S., McMichael A. J. Complete nucleotide sequence of a unique HLA class I C locus product expressed on the human choriocarcinoma cell line BeWo. J Immunol. 1989 May 1;142(9):3281–3285. [PubMed] [Google Scholar]
  9. Faulk W. P., Temple A. Distribution of beta2 microglobulin and HLA in chorionic villi of human placentae. Nature. 1976 Aug 26;262(5571):799–802. doi: 10.1038/262799a0. [DOI] [PubMed] [Google Scholar]
  10. Fehling H. J., Swat W., Laplace C., Kühn R., Rajewsky K., Müller U., von Boehmer H. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science. 1994 Aug 26;265(5176):1234–1237. doi: 10.1126/science.8066463. [DOI] [PubMed] [Google Scholar]
  11. Früh K., Yang Y., Arnold D., Chambers J., Wu L., Waters J. B., Spies T., Peterson P. A. Alternative exon usage and processing of the major histocompatibility complex-encoded proteasome subunits. J Biol Chem. 1992 Nov 5;267(31):22131–22140. [PubMed] [Google Scholar]
  12. Goodfellow P. N., Barnstable C. J., Bodmer W. F., Snary D., Crumpton M. J. Expression of HLA system antigens on placenta. Transplantation. 1976 Dec;22(6):595–603. doi: 10.1097/00007890-197612000-00009. [DOI] [PubMed] [Google Scholar]
  13. Hager H., Aboagye-Mathiesen G., Petersen P. M., Nørskov-Lauritsen N., Juhl C. B., Villadsen J. A., Zdravkovic M., Gildberg A., Dalsgaard A. M., Ebbesen P. Human trophoblast interferons enhance major histocompatibility complex class I antigen expression on human term trophoblast cells in culture. Placenta. 1994 Oct;15(7):709–714. doi: 10.1016/0143-4004(94)90033-7. [DOI] [PubMed] [Google Scholar]
  14. Hsi B. L., Yeh C. J., Faulk W. P. Class I antigens of the major histocompatibility complex on cytotrophoblast of human chorion laeve. Immunology. 1984 Aug;52(4):621–629. [PMC free article] [PubMed] [Google Scholar]
  15. Hunt J. S., Andrews G. K., Wood G. W. Normal trophoblasts resist induction of class I HLA. J Immunol. 1987 Apr 15;138(8):2481–2487. [PubMed] [Google Scholar]
  16. Hunt J. S., Fishback J. L., Chumbley G., Loke Y. W. Identification of class I MHC mRNA in human first trimester trophoblast cells by in situ hybridization. J Immunol. 1990 Jun 1;144(11):4420–4425. [PubMed] [Google Scholar]
  17. Hunt J. S., Orr H. T. HLA and maternal-fetal recognition. FASEB J. 1992 Mar;6(6):2344–2348. doi: 10.1096/fasebj.6.6.1544544. [DOI] [PubMed] [Google Scholar]
  18. Kovats S., Main E. K., Librach C., Stubblebine M., Fisher S. J., DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990 Apr 13;248(4952):220–223. doi: 10.1126/science.2326636. [DOI] [PubMed] [Google Scholar]
  19. Martinez C. K., Monaco J. J. Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene. Nature. 1991 Oct 17;353(6345):664–667. doi: 10.1038/353664a0. [DOI] [PubMed] [Google Scholar]
  20. Mitchell M. D., Trautman M. S., Dudley D. J. Cytokine networking in the placenta. Placenta. 1993 May-Jun;14(3):249–275. doi: 10.1016/s0143-4004(05)80426-6. [DOI] [PubMed] [Google Scholar]
  21. Palombella V. J., Rando O. J., Goldberg A. L., Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994 Sep 9;78(5):773–785. doi: 10.1016/s0092-8674(94)90482-0. [DOI] [PubMed] [Google Scholar]
  22. Restifo N. P., Esquivel F., Kawakami Y., Yewdell J. W., Mulé J. J., Rosenberg S. A., Bennink J. R. Identification of human cancers deficient in antigen processing. J Exp Med. 1993 Feb 1;177(2):265–272. doi: 10.1084/jem.177.2.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roby K. F., Fei K., Yang Y., Hunt J. S. Expression of HLA class II-associated peptide transporter and proteasome genes in human placentas and trophoblast cell lines. Immunology. 1994 Nov;83(3):444–448. [PMC free article] [PubMed] [Google Scholar]
  24. Roby K. F., Hunt J. S. Mouse endometrial tumor necrosis factor-alpha messenger ribonucleic acid and protein: localization and regulation by estradiol and progesterone. Endocrinology. 1994 Dec;135(6):2780–2789. doi: 10.1210/endo.135.6.7988471. [DOI] [PubMed] [Google Scholar]
  25. Sanders S. K., Giblin P. A., Kavathas P. Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts. J Exp Med. 1991 Sep 1;174(3):737–740. doi: 10.1084/jem.174.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schmidt C. M., Orr H. T. Maternal/fetal interactions: the role of the MHC class I molecule HLA-G. Crit Rev Immunol. 1993;13(3-4):207–224. [PubMed] [Google Scholar]
  27. Shorter S. C., Starkey P. M., Ferry B. L., Clover L. M., Sargent I. L., Redman C. W. Antigenic heterogeneity of human cytotrophoblast and evidence for the transient expression of MHC class I antigens distinct from HLA-G. Placenta. 1993 Sep-Oct;14(5):571–582. doi: 10.1016/s0143-4004(05)80210-3. [DOI] [PubMed] [Google Scholar]
  28. Sunderland C. A., Redman C. W., Stirrat G. M. HLA A, B, C antigens are expressed on nonvillous trophoblast of the early human placenta. J Immunol. 1981 Dec;127(6):2614–2615. [PubMed] [Google Scholar]
  29. Treier M., Staszewski L. M., Bohmann D. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain. Cell. 1994 Sep 9;78(5):787–798. doi: 10.1016/s0092-8674(94)90502-9. [DOI] [PubMed] [Google Scholar]
  30. Yang Y., Waters J. B., Früh K., Peterson P. A. Proteasomes are regulated by interferon gamma: implications for antigen processing. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4928–4932. doi: 10.1073/pnas.89.11.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yang Y., Yelavarthi K. K., Chen H. L., Pace J. L., Terranova P. F., Hunt J. S. Molecular, biochemical, and functional characteristics of tumor necrosis factor-alpha produced by human placental cytotrophoblastic cells. J Immunol. 1993 Jun 15;150(12):5614–5624. [PubMed] [Google Scholar]
  32. Yelavarthi K. K., Fishback J. L., Hunt J. S. Analysis of HLA-G mRNA in human placental and extraplacental membrane cells by in situ hybridization. J Immunol. 1991 Apr 15;146(8):2847–2854. [PubMed] [Google Scholar]
  33. Yewdell J., Lapham C., Bacik I., Spies T., Bennink J. MHC-encoded proteasome subunits LMP2 and LMP7 are not required for efficient antigen presentation. J Immunol. 1994 Feb 1;152(3):1163–1170. [PubMed] [Google Scholar]
  34. Zanelli E., Zhou P., Cao H., Smart M. K., David C. S. Genomic organization and tissue expression of the mouse proteasome gene Lmp-7. Immunogenetics. 1993;38(6):400–407. doi: 10.1007/BF00184520. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES