Hypercapnia occurs when the partial pressure of carbon dioxide (CO2) in the blood exceeds 45 mmHg. Hypercapnia is associated with several lung pathologies and is transcriptionally linked to suppression of immune and inflammatory signalling through poorly understood mechanisms. Here we propose Orphan Nuclear Receptor Family 4A (NR4A) family members NR4A2 and NR4A3 as potential transcriptional regulators of the cellular response to hypercapnia in monocytes. Using a THP-1 monocyte model, we investigated the sensitivity of NR4A family members to CO2 and the impact of depleting NR4A2 and NR4A3 on the monocyte response to buffered hypercapnia (10% CO2) using RNA-sequencing. We observed that NR4A2 and NR4A3 are CO2-sensitive transcription factors and that depletion of NR4A2 and NR4A3 led to reduced CO2-sensitivity of mitochondrial and heat shock protein (Hsp)-related genes, respectively. Several CO2-sensitive genes were, however, refractory to depletion of NR4A2 and NR4A3, indicating that NR4As regulate certain elements of the cellular response to buffered hypercapnia but that other transcription factors also contribute. Bioinformatic analysis of conserved CO2-sensitive genes implicated several novel putative CO2-sensitive transcription factors, of which the ETS Proto-Oncogene 1 Transcription Factor (ETS-1) was validated to show increased nuclear expression in buffered hypercapnia. These data give significant insights into the understanding of immune responses in patients experiencing hypercapnia.
机构:
Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands
Pols, Thijs W. H.
Bonta, Peter I.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands
Bonta, Peter I.
de Vries, Carlie J. M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands
机构:
Univ Alberta, Dept AFNS, Edmonton, AB T6G 2E1, Canada
Li Ka Shing Ctr, Alberta Diabet Inst, Edmonton, AB T6G 2E1, CanadaUniv Alberta, Dept AFNS, Edmonton, AB T6G 2E1, Canada
机构:
Univ Alberta, Dept AFNS, Edmonton, AB T6G 2E1, Canada
Li Ka Shing Ctr, Alberta Diabet Inst, Edmonton, AB T6G 2E1, CanadaUniv Alberta, Dept AFNS, Edmonton, AB T6G 2E1, Canada
机构:
Univ Kansas, Med Ctr, Div Med Oncol, Fairway, KS USA
Tulane Univ, Sch Med, Hematol Oncol Sect, 1430 Tulane Ave,8078, New Orleans, LA 70112 USAUniv Kansas, Med Ctr, Div Med Oncol, Fairway, KS USA
Komiya, Takefumi
Yamamoto, Satomi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Kansas, Med Ctr, Div Med Oncol, Fairway, KS USAUniv Kansas, Med Ctr, Div Med Oncol, Fairway, KS USA
Yamamoto, Satomi
Roy, Anuradha
论文数: 0引用数: 0
h-index: 0
机构:
Univ Kansas, Sch Pharm, High Throughput Screening Facil, Lawrence, KS 66045 USAUniv Kansas, Med Ctr, Div Med Oncol, Fairway, KS USA
Roy, Anuradha
McDonald, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Univ Kansas, Sch Pharm, High Throughput Screening Facil, Lawrence, KS 66045 USAUniv Kansas, Med Ctr, Div Med Oncol, Fairway, KS USA
McDonald, Peter
Perez, Raymond P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Kansas, Med Ctr, Div Med Oncol, Fairway, KS USAUniv Kansas, Med Ctr, Div Med Oncol, Fairway, KS USA
机构:
Charles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Biopt Lab Ltd, Plzen, Czech Republic
Charles Univ Prague, Biomed Ctr, Fac Med Pilsen, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Klubickova, Natalie
Grossmann, Petr
论文数: 0引用数: 0
h-index: 0
机构:
Biopt Lab Ltd, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Grossmann, Petr
Steiner, Petr
论文数: 0引用数: 0
h-index: 0
机构:
Biopt Lab Ltd, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Steiner, Petr
Baneckova, Martina
论文数: 0引用数: 0
h-index: 0
机构:
Charles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Biopt Lab Ltd, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Baneckova, Martina
Mosaieby, Elaheh
论文数: 0引用数: 0
h-index: 0
机构:
Charles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Biopt Lab Ltd, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Mosaieby, Elaheh
Koshyk, Olena
论文数: 0引用数: 0
h-index: 0
机构:
Med Lab CSD, Kiev, UkraineCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Koshyk, Olena
Michal, Michal
论文数: 0引用数: 0
h-index: 0
机构:
Charles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Biopt Lab Ltd, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Michal, Michal
Leivo, Ilmo
论文数: 0引用数: 0
h-index: 0
机构:
Univ Turku, Inst Biomed, Pathol, Turku, Finland
Turku Univ Hosp, Dept Pathol, Turku, FinlandCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Leivo, Ilmo
Skalova, Alena
论文数: 0引用数: 0
h-index: 0
机构:
Charles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic
Biopt Lab Ltd, Plzen, Czech RepublicCharles Univ Prague, Fac Med Pilsen, Dept Pathol, Plzen, Czech Republic