Estrogenic Regulation of Inflammation Related to TMJD

Summary

Principal Investigator: Phillip Kramer
Abstract: Our long-range goal is to identify and characterize genes through which steroidal hormones affect the onset and/or severity of human disease. The objective of this application is to determine a gene in macrophages affected by estrogen withdrawal, as seen post-partum and at menopause, that functions in immune processes. Our central hypothesis is that changes in estrogen concentrations directly regulate IgG Fc gamma receptor III-A (CD16a) expression resulting in a modulation of pro-inflammatory cytokine production and/or release from macrophages upon receptor binding. This hypothesis is based on our recent findings in vitro that 1) the level of Fc gamma RIIIA transcript increased in macrophage-like THP-1 cells and in primary, peripheral blood macrophages after estrogen removal and 2) that the observed increase was dependent on transcription. The hypothesis also includes data from another lab that binding of Fc gamma RIIIA by anti-Fc gamma RIll monoclonal antibodies stimulates macrophage TNF-alpha and IL-1 alpha release. Fc gamma RIIIA is a receptor that selectively binds IgG molecules, an important rheumatoid factor (RF) in auto-immune disease. Collectively, these data suggest that RF binding of this receptor stimulates cytokine release in rheumatoid arthritis and associated temporomandibular joint disorders (TMJD). To test our central hypothesis aim one will characterize macrophage cytokine production and release from stimulated macrophages after modulating Fc gamma RIIIA expression. TNF-alpha and IL-1 alpha will be measured after changing Fc gamma RIIIA expression levels using various estrogen and Fc gamma RIIIA antisense treatments. Aim two will focus on the mechanism inducing cytokine production and/or release upon Fc gamma RIIIA crosslinking. Signal transduction pathways and activated transcription factors will be identified as well as regulatory TNF-alpha and IL-1 alpha promoter sequences. Aim three will address the mechanism by which estrogen regulates Fc gamma RIIIA gene transcription in macrophages. The function of estrogen receptors ER alpha and/or ER beta will be directly addressed pharmacologically (e.g., antiestrogen) and through mutation studies of the Fc gamma RIIIA promoter.
Funding Period: 2003-07-15 - 2008-05-31
more information: NIH RePORT

Top Publications

  1. pmc A non-invasive model for measuring nociception after tooth pulp exposure
    P R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, Dallas, TX 75246, USA
    J Dent Res 91:883-7. 2012
  2. pmc Reduced GABA(A) receptor α6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity
    J Puri
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA
    Neuroscience 213:179-90. 2012
  3. pmc Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction
    Jyoti Puri
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, Texas 75246, USA
    J Cell Physiol 226:3169-80. 2011
  4. pmc Knockdown of Fcγ receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats
    Phillip R Kramer
    Texas A and M Health Science Center and Baylor College of Dentistry, Dallas TX USA
    Arthritis Rheum 62:3109-18. 2010
  5. pmc Measuring persistent temporomandibular joint nociception in rats and two mice strains
    Phillip R Kramer
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, TX 75246, USA
    Physiol Behav 99:669-78. 2010
  6. pmc Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint
    Jyoti Puri
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, Texas, USA
    Reprod Biol Endocrinol 7:155. 2009
  7. pmc The effects of cycling levels of 17beta-estradiol and progesterone on the magnitude of temporomandibular joint-induced nociception
    P R Kramer
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, Texas 75246, USA
    Endocrinology 150:3680-9. 2009
  8. ncbi Integrin mediated attachment of periodontal ligament to titanium surfaces
    Phillip R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M University System Health Science Center, 3302 Gaston Avenue, Dallas, TX 75246, USA
    Dent Mater 25:877-83. 2009
  9. pmc PI3K limits TNF-alpha production in CD16-activated monocytes
    Phillip R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, Dallas, TX 75246, USA
    Eur J Immunol 39:561-70. 2009
  10. ncbi Selective blockade of the rat brain aqueduct with thermogelling hydrogel nanoparticle dispersion
    Phillip R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M University System Health Science Center, Dallas, TX 75246, USA
    Physiol Behav 93:546-52. 2008

Scientific Experts

Detail Information

Publications13

  1. pmc A non-invasive model for measuring nociception after tooth pulp exposure
    P R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, Dallas, TX 75246, USA
    J Dent Res 91:883-7. 2012
    ..Evidence supports that a lengthening in meal duration is a response to tooth nociception and that this nociception can be measured for over a week...
  2. pmc Reduced GABA(A) receptor α6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity
    J Puri
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA
    Neuroscience 213:179-90. 2012
    ..These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception...
  3. pmc Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction
    Jyoti Puri
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, Texas 75246, USA
    J Cell Physiol 226:3169-80. 2011
    ..These results demonstrate that genes associated with neurogenic inflammation or neuronal excitability were altered by changes in the concentration of 17β-estradiol...
  4. pmc Knockdown of Fcγ receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats
    Phillip R Kramer
    Texas A and M Health Science Center and Baylor College of Dentistry, Dallas TX USA
    Arthritis Rheum 62:3109-18. 2010
    ..We undertook this study to test the hypothesis that a reduction in FcγRIII expression in TMJ tissues would reduce the nociceptive and inflammatory responses in an inflamed joint...
  5. pmc Measuring persistent temporomandibular joint nociception in rats and two mice strains
    Phillip R Kramer
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, TX 75246, USA
    Physiol Behav 99:669-78. 2010
    ..In addition, C57Bl/6 mice are resistant to CFA-induced TMJ nociception at the same dose used in the DBA/1LacJ mice...
  6. pmc Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint
    Jyoti Puri
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, Texas, USA
    Reprod Biol Endocrinol 7:155. 2009
    ..In this study, ERalpha protein content and the number of cells expressing ERalpha was measured in 17 beta-estradiol-treated rats after inflammation was induced in the TMJ...
  7. pmc The effects of cycling levels of 17beta-estradiol and progesterone on the magnitude of temporomandibular joint-induced nociception
    P R Kramer
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, Dallas, Texas 75246, USA
    Endocrinology 150:3680-9. 2009
    ..The results suggest that the cyclic estrous cycle concentrations of E2 and P4 can influence CFA-induced TMJ nociception in the rat...
  8. ncbi Integrin mediated attachment of periodontal ligament to titanium surfaces
    Phillip R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M University System Health Science Center, 3302 Gaston Avenue, Dallas, TX 75246, USA
    Dent Mater 25:877-83. 2009
    ..To begin to pursue the goal of creating a periodontal ligament interface between a dental implant and bone, the mechanism of cellular attachment to dental implant surfaces must be characterized...
  9. pmc PI3K limits TNF-alpha production in CD16-activated monocytes
    Phillip R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, Dallas, TX 75246, USA
    Eur J Immunol 39:561-70. 2009
    ..The results suggest that CD16 cross-linking activated PI3K and that active PI3K limited TNF-alpha production by inhibiting GSK-3beta activity, that blocked the action of NF-kappaB...
  10. ncbi Selective blockade of the rat brain aqueduct with thermogelling hydrogel nanoparticle dispersion
    Phillip R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M University System Health Science Center, Dallas, TX 75246, USA
    Physiol Behav 93:546-52. 2008
    ..We conclude that isolation of ventricles in the brain can be completed for 48-h by using dispersions of hydrogel nanoparticles and the effects of drugs on certain brain tissues can be determined with this method...
  11. pmc 17beta-Estradiol utilizes the estrogen receptor to regulate CD16 expression in monocytes
    P R Kramer
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M University Health Science Center, 3302 Gaston Avenue, Dallas, TX 75246, USA
    Mol Cell Endocrinol 279:16-25. 2007
    ..In conclusion, CD16 expression can be altered by the activity of ERalpha or ERbeta and our results also show that ERalpha can associate with a region within the CD16 promoter that is important in production of transcript...
  12. ncbi Capsaicin sensitive neurons role in the inflamed TMJ acute nociceptive response of female and male rats
    Larry L Bellinger
    Department of Biomedical Sciences, Texas A and M Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, Texas 75246, United States
    Physiol Behav 90:782-9. 2007
    ..The data suggests CAP-sensitive neurons are responsible, in part, for transmission of acute nociceptive responses associated with CFA administration and suggest gender can affect nociception in the inflamed TMJ region...
  13. ncbi Estrogenic effect on swelling and monocytic receptor expression in an arthritic temporomandibular joint model
    Guoqiang Guan
    Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M University System, Health Science Center, Dallas, 75246, USA
    J Steroid Biochem Mol Biol 97:241-50. 2005
    ..Estrogenic group differences in CFA induced swelling were independent of TMJ CD14+, CD14+/CD16+ or CD16+ cell numbers suggesting E2 action on the CFA immune response primarily excluded CD16 receptor action...