The low molecular weight fraction of human serum albumin upregulates production of 15d-PGJ2 in Peripheral Blood Mononuclear Cells.
Activation of the innate immune system involves a series of events designed to counteract the initial insult followed by the clearance of debris and promotion of healing. Aberrant regulation can lead to systemic inflammatory response syndrome, multiple organ failure, and chronic inflammation. A better understanding of the innate immune response may help manage complications while allowing for proper immune progression. In this study, the ability of several classes of anti-inflammatory drugs to affect LPS-induced cytokine and prostaglandin release from peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were cultured in the presence of dexamethasone (DEX), ibuprofen (IBU), and the low molecular weight fraction of 5% albumin (LMWF5A) followed by stimulation with LPS. After 24 h, TNFα, PGE2, and 15d-PGJ2 release was determined by ELISA. Distinct immunomodulation patterns emerged following LPS stimulation of PBMC in the presence of said compounds. DEX, a steroid with strong immunosuppressive properties, reduced TNFα, PGE2, and 15d-PGJ2 release. IBU caused significant reduction in prostaglandin release while TNFα release was unchanged. An emerging biologic with known anti-inflammatory properties, LMWF5A, significantly reduced TNFα release while enhancing PGE2 and 15d-PGJ2 release. Incubating LMWF5A together with IBU negated this observed increased prostaglandin release without affecting the suppression of TNFα release. Additionally, LMWF5A caused an increase in COX-2 transcription and translation. LMWF5A exhibited a unique immune modulation pattern in PBMC, disparate from steroid or NSAID administration. This enhancement of prostaglandin release (specifically 15d-PGJ2), in conjunction with a decrease in TNFα release, suggests a switch that favors resolution and decreased inflammation.
Swedish Medical Center, 501 E. Hampden Ave., Englewood, CO 80113, USA; St. Anthony Hospital, 11600 W. 2nd, Pl., Lakewood, CO 80228, USA; The Medical Center of Plano, 3901 W. 15th, St., Plano, TX 75075, USA. Electronic address: gthomas@ampiopharma.com.
Gregory W
GW
Thomas
Swedish Medical Center, 501 E. Hampden Ave., Englewood, CO 80113, USA; St. Anthony Hospital, 11600 W. 2nd, Pl., Lakewood, CO 80228, USA; The Medical Center of Plano, 3901 W. 15th, St., Plano, TX 75075, USA. Electronic address: lrael@ampiopharma.com.
Leonard T
LT
Rael
Swedish Medical Center, 501 E. Hampden Ave., Englewood, CO 80113, USA; St. Anthony Hospital, 11600 W. 2nd, Pl., Lakewood, CO 80228, USA; The Medical Center of Plano, 3901 W. 15th, St., Plano, TX 75075, USA. Electronic address: mhausburg@ampiopharma.com.
Melissa
M
Hausburg
Swedish Medical Center, 501 E. Hampden Ave., Englewood, CO 80113, USA; St. Anthony Hospital, 11600 W. 2nd, Pl., Lakewood, CO 80228, USA; The Medical Center of Plano, 3901 W. 15th, St., Plano, TX 75075, USA. Electronic address: efrederick@ampiopharma.com.
Elizabeth D
ED
Frederick
St. Anthony Hospital, 11600 W. 2nd, Pl., Lakewood, CO 80228, USA. Electronic address: CharlesMains@centura.org.
Charles W
CW
Mains
Swedish Medical Center, 501 E. Hampden Ave., Englewood, CO 80113, USA. Electronic address: sue.slone@healthonecares.com.
Denetta
D
Slone
The Medical Center of Plano, 3901 W. 15th, St., Plano, TX 75075, USA. Electronic address: matt.carrick@acutesurgical.com.
Matthew M
MM
Carrick
Swedish Medical Center, 501 E. Hampden Ave., Englewood, CO 80113, USA; St. Anthony Hospital, 11600 W. 2nd, Pl., Lakewood, CO 80228, USA; The Medical Center of Plano, 3901 W. 15th, St., Plano, TX 75075, USA; Rocky Vista University, 8401 S. Chambers Rd., Parker, CO 80134, USA. Electronic address: dbaror@ampiopharma.com.
David
D
Bar-Or
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008970:Molecular Weight; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000276:immunology; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
C477819:15-deoxyprostaglandin J2; D016207:Cytokines; D008070:Lipopolysaccharides; D012709:Serum Albumin; D015230:Prostaglandin D2
Human serum albumin; Lipopolysaccharide; Peripheral blood mononuclear cells; Prostaglandins; Tumor necrosis factor α