Paper
Differential regulation of monocyte/macrophage cytokine production by pressure

Presented at the 29th Annual Surgical Symposium of the Association of VA Surgeons, Salt Lake City, Utah, March 11–13, 2005
https://doi.org/10.1016/j.amjsurg.2005.07.016Get rights and content

Abstract

Background

Cytokine production by macrophages is essential for the inflammatory response. Normal human interstitial tissue pressure is 20 to 30 mm Hg, but generally decreases in acute inflammation.

Methods

We compared the effect of 20 mm Hg increased pressure (approximating normal interstitial tissue pressure) with that of ambient pressure (resembling pressure in inflamed tissues) on tumor necrosis factor (TNF)-α and interleukin (IL)-1β production by undifferentiated (monocytic) and PMA (phorbol 12-, myristate 13-acetate)-differentiated (macrophage-like) THP-1 cells with or without lipopolysaccharide (LPS) (10 ng/mL).

Results

Pressure stimulated spontaneous macrophage TNF-α secretion (30.5 ± 6.3 vs. 49.1 ± 2.8 pg/mL, P <.02), but not monocyte TNF-α secretion. Pressure did not stimulate IL-1β release. As expected, LPS increased basal cytokine release. After LPS stimulation, pressure still tended to stimulate macrophage TNF-α, but inhibited monocyte TNF-α secretion (P <.05). In contrast, pressure inhibited IL-1β release by both LPS-treated monocytes (986 ± 134 vs. 595 ± 226 pg/mL, P <.02) and macrophages (3,112 ± 229 vs. 979 ± 61 pg/mL, P <.01).

Conclusions

Extracellular pressure may regulate TNF-α and IL-1β secretion differentially by monocytes and macrophages.

Section snippets

Cells and cell cultures

The human monocytic cell line THP-1 was obtained from the American Type Culture Collection (Rockville, MD). THP-1 cells were maintained in RPMI-1640 (Gibco, Grand Island, NY), supplemented with 10% fetal bovine serum (Sigma, St. Louis, MO), L-glutamine (200 mmol/L), and 2-mercapto-ethanol (5 × 10−5 mol/L) (Sigma). MonoMac-1 cells were maintained in RPMI-1640 supplemented with 10% fetal bovine serum, L-glutamine (200 mmol/L), nonessential amino acids, and 1 mmol/L sodium pyruvate.

As previously

Pressure effect on cytokine production by THP-1 cells

We previously reported that exposure to constant low (20 mm Hg) extracellular pressure enhanced serum-opsonized latex bead uptake by PMA-differentiated THP-1 macrophages and primary isolated human peripheral monocytes [5], [6]. We now examined the effect of extracellular pressure on TNF-α and IL-1β release from the human THP-1 monocytic cell line. PMA-differentiated (macrophage-like) or unstimulated (monocyte-like) THP-1 cells were cultured under ambient pressure (consistent with extracellular

Comments

Normal interstitial tissue pressure in human beings is 20 to 30 mm Hg and generally decreases in acute infection and inflammation [1], [2], [3], [4]. Although infection or edema in closed compartments may increase tissue pressure by 5 to 80 mm Hg [16], [17], [18], interstitial extracellular pressure generally decreases in infected or inflamed tissue lacking such special conditions. Edema formation in unconstrained inflamed or infected tissues actually may be associated with decreases in

Acknowledgment

Supported in part by National Institutes of Health grant RO1 DK60771 (M.D.B.).

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