Cytokine Networks in the Regulation of Inflammation and Fibrosis in the Lung (Part 5)

In: Pulmonary function

11 Nov 2012

Cytokine-cytokine interactions play an important role in regulating fibroblast collagen production as well as fibroblast proliferation. Under serum-free conditions, rIFN-7 did not consistently alter fibroblast collagen production. However, it did negate the stimulatory effects of rIL-1 (a or P) (Fig 4) or rTNF (data not shown). In addition, combining rIL-1 and rTNF caused fibroblasts to produce less collagen than they did with either cytokine individually (data not shown). Thus, individual cytokines tend to stimulate fibroblast collagen production with cytokine-cytokine combinations tending to inhibit fibroblast collagen production. Buy Asthma Inhalers Online
We proposed that cytokine stimulated fibroblasts produce regulatory moieties that feed back to regulate local inflammatory events. To test this hypothesis, we determined whether fibroblasts produce IL-l-a, IL-1-P, and IL-6. These moieties were chosen because each is known to be produced by a wide variety of cells and to have a wide variety of regulatory functions.’’
Fibroblast IL-l-a
To determine whether fibroblasts produced IL-l-a in response to recombinant cytokines, we determined whether unstimulated or cytokine-stimulated fibroblasts contained cell associated thymocyte-stimulating activity that was able to be neutralized by antiserum against rIL-l-a. Unstimulated fibroblast did not contain thymocyte-stimulating activity. In contrast, rIL-1 (a or p) and rTNF, individually, stimulated fibroblast IL-l-a expression (Table 2). In all cases, the effects of rIL-1 and rTNF, alone and in combination, were dose-dependent and could be negated by preincubating either cytokine with its respective neutralizing antibody. Thus, fibroblast IL-l-a expression also appears to be regulated by individual cytokines and cytokine-cytokine interactions.

Figure_4

Figure 4. Representative experiment demonstrating the effects of rIL-1 and rIFN-7, alone and in combination, on the production of type I collagen by quiescent fibroblasts. Fibroblasts were incubated in the presence and absence of rIFN-“y (500 I.U./ml) and/or rIL-1-a (2.5 mg/ml) as noted. The collagen levels in the resulting supernatants were assessed by RIA. 

 Table 2—Recombinant Cytokine Regulation of Fibroblast Interleukin-1-a 

Fibroblast

Culture

Conditions

Thymocyte 3 H-Tdr Incorporation

Control

2,177 ±1,071

rIL-1

11,333 ±1,094

rTNF

5,155 ±4,776

rIL-1 + rTNF

39,956 ±2,113


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